比特派錢包最新版|mirna

作者: 比特派錢包最新版
2024-03-17 09:28:22

micro RNA_百度百科

o RNA_百度百科網(wǎng)頁新聞貼吧知道網(wǎng)盤圖片視頻地圖文庫資訊采購百科百度首頁登錄注冊進入詞條全站搜索幫助首頁秒懂百科特色百科知識專題加入百科百科團隊權(quán)威合作下載百科APP個人中心micro RNA播報討論上傳視頻生物學(xué)術(shù)語收藏查看我的收藏0有用+10MicroRNA (miRNA) 是一類由內(nèi)源基因編碼的長度約為22 個核苷酸的非編碼單鏈RNA分子，它們在動植物中參與轉(zhuǎn)錄后基因表達調(diào)控。在動植物以及病毒中已經(jīng)發(fā)現(xiàn)有28645個miRNA 分子(Release 21: June 2014) 。大多數(shù)miRNA 基因以單拷貝、多拷貝或基因簇(cluster) 的形式存在于基因組中(Lagos2Quintanaet al, 2001;Lau et al,2001) 。miRNA可以通過破壞靶mRNA的穩(wěn)定性、抑制靶mRNA的翻譯來對靶mRNA發(fā)揮調(diào)控作用。 [4]中文名微小核糖核酸外文名MicroRNA 性????質(zhì)非編碼單鏈RNA分子縮????寫miRNA存在形式單拷貝、多拷貝或基因簇載????體動植物以及病毒目錄1簡介2MicroRNA3特征4功能?MicroRNA的過表達?MicroRNA的下調(diào)5作用方式6識別方法7siRNA8待解決問題9研究工具?分離?探針制備?檢測10功能分析11miRNA展望簡介播報編輯micro RNAMicroRNA (miRNA) 是一類內(nèi)生的、長度約為20-24個核苷酸的小RNA，其在細胞內(nèi)具有多種重要的調(diào)節(jié)作用。每個miRNA可以有多個靶基因，而幾個miRNA也可以調(diào)節(jié)同一個基因。這種復(fù)雜的調(diào)節(jié)網(wǎng)絡(luò)既可以通過一個miRNA來調(diào)控多個基因的表達，也可以通過幾個miRNA的組合來精細調(diào)控某個基因的表達。據(jù)推測，miRNA調(diào)節(jié)著人類三分之一的基因。最近的研究表明大約70 %的哺乳動物miRNA 是位于TUs區(qū)( transcriptionunits , TUs ) ( Rodriguez et al ,2004) , 且其中大部分是位于內(nèi)含子區(qū)( Kim &Nam , 2006) 。一些內(nèi)含子miRNA 的位置在不同的物種中是高度保守的。miRNA 不僅在基因位置上保守, 序列上也呈現(xiàn)出高度的同源性(Pasquinelli etal , 2000 ; Ruvkun et al , 2001 ; Lee & Ambros ,2001) 。miRNA 高度的保守性與其功能的重要性有著密切的關(guān)系。miRNA 與其靶基因的進化有著密切的聯(lián)系, 研究其進化歷史有助于進一步了解其作用機制和功能。MicroRNA播報編輯MicroRNA（miRNA）是一類內(nèi)生的、長度約20-24個核苷酸的小RNA，幾個miRNAs也可以調(diào)節(jié)同一個基因?？梢酝ㄟ^幾個miRNAs的組合來精細調(diào)控某個基因的表達。據(jù)推測，miRNA調(diào)節(jié)著人類三分之一的基因。MicroRNA存在多種形式，最原始的是pri-miRNA，長度大約為300~1000個堿基；pri-miRNA經(jīng)過一次加工后，成為pre-miRNA即microRNA前體，長度大約為70~90個堿基；pre-miRNA再經(jīng)過Dicer酶酶切后，成為長約20~24nt的成熟miRNA。實際研究中，pre-miRNA應(yīng)用最早，也最廣泛，很多商業(yè)化的MicroRNA庫都是pre-miRNA形式的。近幾年來，研究發(fā)現(xiàn)microRNA的雙臂對成熟miRNA的形成有著十分重要的作用，所以天然的pri-miRNA形式越來越多地被研究者采用。MicroRNAs（miRNAs）是一種大小約21—23個堿基的單鏈小分子RNA，是由具有發(fā)夾結(jié)構(gòu)的約70-90個堿基大小的單鏈RNA前體經(jīng)過Dicer酶加工后生成，不同于siRNA（雙鏈）但是和siRNA密切相關(guān)。據(jù)推測，這些非編碼小分子RNA（miRNAs）參與調(diào)控基因表達，但其機制區(qū)別于siRNA介導(dǎo)的mRNA降解。第一個被確認的miRNA是在線蟲中首次發(fā)現(xiàn)的lin-4 和let-7，隨后多個研究小組在包括人類、果蠅、植物等多種生物物種中鑒別出數(shù)百個miRNAs。特征播報編輯已經(jīng)被鑒定的miRNAs據(jù)推測大都是由具有發(fā)夾結(jié)構(gòu)，約70個堿基大小形成發(fā)夾結(jié)構(gòu)的單鏈RNA前體經(jīng)過Dicer酶加工后生成的，有5’端磷酸基和3’羥基，大小約21—25nt的小分子RNA片段，定位于RNA前體的3’端或者5’端。3個研究小組分別從線蟲、果蠅和Hela細胞中鑒定的100個新miRNAs中，有15%跨越線蟲、果蠅和哺乳動物基因組具有高度的保守性（只有有1—2個堿基的區(qū)別）。Lau 和Bartel 實驗室的同事更加認為：所有的miRNAs可能在其他物種中具有直向同源物（Ortholog，指那些起源于同一祖先，在不同生物體中行使同一功能的基因群就可比作為一個門類，這些類似的基因被稱為“直向同源物”）。micro RNABantam 最早被認為是果蠅中參與細胞增殖的一個基因位點。已知幾個包含增強子的轉(zhuǎn)座子插入跨越這個位點的一段12.3kb區(qū)域會導(dǎo)致果蠅的眼和翅重復(fù)生長，而由轉(zhuǎn)座子介導(dǎo)的一段跨越該位點的23kb片斷缺失則導(dǎo)致突變果蠅個體小于野生型果蠅。Cohen和同事用一段3.85kb的片斷導(dǎo)入21kb片斷缺失的果蠅中使其恢復(fù)原來的大小。但是奇怪的是表達這個3.85kb片斷中的EST卻沒有同樣的效果。Cohen將這個片斷和瘧蚊Anopheles gambiae的同源序列進行比較，發(fā)現(xiàn)一段90bp的高度保守區(qū)，經(jīng)過RNA folding program (mfold)發(fā)現(xiàn)這個保守序列可以形成發(fā)夾結(jié)構(gòu)，使得這個區(qū)段很象是一個miRNA的前體。這個結(jié)果經(jīng)過Northern blot證實突變果蠅的幼體缺少一個21bp的bantam miRNA ，用這個90bp的mRNA前體經(jīng)過一系列的“功能缺失”—“功能恢復(fù)”實驗，證實 bantam miRNA在細胞增殖中的作用。研究人員用計算機程序檢索在hid mRNA的3’非編碼區(qū)找到了bantam的3個潛在的結(jié)合位點（ hid是果蠅中一個誘導(dǎo)凋亡的基因），并證實 bantam miRNA抑制hid 的翻譯而非轉(zhuǎn)錄。miRNAs的表達方式各不相同。部分線蟲和果蠅的miRNA在各個發(fā)育階段的全部細胞中都有表達，而其他的miRNA則依據(jù)某種更為嚴謹?shù)奈幌嗪蜁r相的表達模式（a more restricted spatial and temporal expression pattern）——在不同組織、不同發(fā)育階段中miRNA的水平有顯著差異。功能播報編輯科學(xué)家開始認識到這些普遍存在的小分子在真核基因表達調(diào)控中有著廣泛的作用。在線蟲，果蠅，小鼠和人等物種中已經(jīng)發(fā)現(xiàn)的數(shù)百個miRNAs中的多數(shù)具有和其他參與調(diào)控基因表達的分子一樣的特征——在不同組織、不同發(fā)育階段中miRNA的水平有顯著差異，這種miRNAs表達模式具有分化的位相性和時序性（differential spatial and temporal expression patterns），提示miRNAs有可能作為參與調(diào)控基因表達的分子，因而具有重要意義。第一個被確認的miRNA——在線蟲中首次發(fā)現(xiàn)的lin-4和let-7，可以通過部分互補結(jié)合到目的mRNA靶的3’非編碼區(qū)(3’UTRs)，以一種未知方式誘發(fā)蛋白質(zhì)翻譯抑制，進而抑制蛋白質(zhì)合成，通過調(diào)控一組關(guān)鍵mRNAs的翻譯從而調(diào)控線蟲發(fā)育進程(reviewed in Pasquinelli 2002)。bantam miRNA是第一個被發(fā)現(xiàn)有原癌基因作用的miRNA。除了lin-4、let-7，已知還有一些miRNAs可能參與在細胞分化和組織發(fā)育過程中起重要作用的基因的轉(zhuǎn)錄后調(diào)控，例如mir-14、mir-23 等。在植物miRNAs的研究中有兩條線索提示miRNAs可能參與植物的發(fā)育過程。一是在carpel factory (car) 突變株中3個miRNAs的表達水平顯著下降。CARPEL FACTORY 是一個類似Dicer的酶，參與植物的發(fā)育，其缺失突變株表現(xiàn)為胚胎和葉片發(fā)育的缺陷。實驗結(jié)果提示這種缺陷是由于缺少miRNAs加工而造成的。多數(shù)的植物miRNAs在某些特定組織中高水平表達也提示他們可能參與了植物組織的發(fā)育。對一部分miRNAs的研究分析提示：miRNAs參與生命過程中一系列的重要進程，包括早期發(fā)育(Reinhart 2000)，細胞增殖，細胞凋亡，細胞死亡(Brennecke 2003)，脂肪代謝(Xu 2003)和細胞分化(Kawasaki 2003)。此外，一個研究表明，2個miRNAs水平的下降和慢性淋巴細胞白血病之間的顯著相關(guān)，提示miRNAs和癌癥之間可能有潛在的關(guān)系(Calin 2002)。由于miRNAs存在的廣泛性和多樣性，提示miRNAs可能有非常廣泛多樣的生物功能。盡管對miRNA的研究還處于初級階段，據(jù)推測miRNAs在高級真核生物體內(nèi)對基因表達的調(diào)控作用可能和轉(zhuǎn)錄因子一樣重要。有一種看法是：miRNAs可能代表在一個新發(fā)現(xiàn)的層次上的基因表達調(diào)控方式。然而，大多數(shù)miRNAs的功能仍然是個謎。MicroRNA的過表達MicroRNA的過表達MicroRNA存在多種形式，最原始的是pri-miRNA ，長度大約為300-1000個堿基pri-miRNA經(jīng)過一次加工后，成為pre-miRNA 即microRNA前體，長度大約為70-90個堿基；pre-miRNA再經(jīng)過Dicer酶酶切后，成為長約20-24nt的成熟miRNA 。實際研究中，pre-miRNA應(yīng)用最早，也最廣泛，目前很多商業(yè)化的MicroRNA庫都是pre-miRNA形式的。近幾年來，研究發(fā)現(xiàn)microRNA的雙臂對成熟miRNA的形成有著十分重要的作用，所以天然的pri-miRNA形式越來越多地被研究者采用。MicroRNA的下調(diào)化學(xué)合成的miRNA inhibitors，用于下調(diào)目的細胞中的miRNA，以實現(xiàn)loss-of function研究。如果您需要進行長期、穩(wěn)定的miRNA下調(diào)，則可以選用載體形式的miRNA inhibitor。其轉(zhuǎn)染效率高，下調(diào)效果好，可以實現(xiàn)對目的miRNA的長期、穩(wěn)定的下調(diào)。MicroRNA的下調(diào)載體形式的miRNA inhibitor，采用的方法如miRNA sponge法，這也是目前SCI文獻中用的較多的一種方法。作用方式播報編輯microRNA-RISC對靶基因mRNA的作用主要取決于它與靶基因轉(zhuǎn)錄體序列互補的程度，有三種方式。第一種是切斷靶基因的mRNA分子——miRNA與靶基因完全互補結(jié)合，作用方式和功能與siRNA非常相似，最后切割靶mRNA。在植物中，大部分miRNA都以這種方式，靶基因mRNA斷裂后，無poly(A)的分子的3‘ 端加上多個U并很快降解，含poly(A)的分子能穩(wěn)定存在一段時間（如擬南芥miR-171）。在植物中目前有一個miRNA和3個潛在的目標(biāo)靶基因完全互補（這些scarecrow 基因編碼潛在的轉(zhuǎn)錄因子），盡管還不清楚這些基因是否就是miRNA的目標(biāo)靶，這仍是第一次發(fā)現(xiàn)miRNA 和其潛在的目標(biāo)靶完全互補，也提示miRNA可能包含和siRNA類似的作用方式。第二種是抑制靶基因的翻譯——作用時與靶基因不完全互補結(jié)合，進而阻遏翻譯而不影響mRNA的穩(wěn)定性，這種miRNA是目前發(fā)現(xiàn)最多的種類（如線蟲lin-4）。而在植物中極少數(shù)的miRNA通過此方式來抑制靶基因。第三種是結(jié)合抑制——具有以上兩種作用模式：當(dāng)與靶基因互補結(jié)合時，直接靶向切割mRNA；當(dāng)與靶基因不完全結(jié)合時，起調(diào)節(jié)基因表達的作用。識別方法播報編輯多個研究小組采用生物化學(xué)結(jié)合以及生物信息學(xué)的方法開展對miRNAs的研究工作。由于據(jù)推測都是由Dicer酶降解RNA得到的，21—23個堿基大小、有5’端磷酸基和3’羥基的RNA片段，有的實驗室采用改良的定向克隆方法來篩選具有相同特征的小分子——篩選一定大小的RNA分子，連接到3’和5’的適配子（adapters），逆轉(zhuǎn)錄并通過PCR擴增、亞克隆并測序。miRNA前體在基因組上的定位和聚類是通過向基因組數(shù)據(jù)庫查詢進行。這個方法有助于判斷miRNAs是否是mRNAs、tRNAs、rRNAs等分子的降解產(chǎn)物。有的實驗室通過一種RNA folding program ’mfold’ 來判斷C. elegans 和C. briggsae 之間的高度保守區(qū)域是否含有潛在的miRNA前體，然后用Northern Blots的方法來確定這些miRNAs是否真的表達了。盡管有數(shù)百個miRNAs通過生化或者是生物信息學(xué)的方法被鑒別出來，已經(jīng)鑒別出來的miRNAs只不過是滄海一粟，由于很多已經(jīng)鑒別出來的miRNAs是從單個克隆中鑒別出來的，所以可以假設(shè)還有很多miRNAs在分離和鑒定過程中被“漏掉”了，測序工作還遠遠不夠。siRNA播報編輯miRNA和siRNA之間的關(guān)系令人迷惑。從表面上說，一個是非編碼的單鏈小分子RNA，在進化上高度保守，通過翻譯抑制調(diào)控基因表達；另一個是針對編碼區(qū)的雙鏈小分子RNA，每個轉(zhuǎn)錄本都可能有很多個siRNAs，是通過降解目標(biāo)靶，在轉(zhuǎn)錄后調(diào)控基因表達。由于每個mRNA模版可能產(chǎn)生很多個siRNAs，要給每個siRNA定一個基因的名字就很困難。miRNA是進化進程中高度保守的，因此給直向同源物一個同樣的名字可能有助于了解他們的功能，而給另一個物種中一段無關(guān)的序列一個同樣的名字就容易造成混亂。然而，據(jù)推測miRNAs通常是由較大的（70--90 nt）的莖環(huán)結(jié)構(gòu)（發(fā)夾結(jié)構(gòu)）前體經(jīng)Dicer酶切割得到的，而Dicer同樣負責(zé)將長雙鏈RNA切割為siRNA，而且二者的長度也差不多，同樣有調(diào)控基因表達功能。因而這兩類小分子RNA之間的關(guān)系格外令人關(guān)注。兩個廣為人知的miRNA——在線蟲中首次發(fā)現(xiàn)的lin-4 和let-7，通過一種未知方式誘發(fā)蛋白質(zhì)翻譯抑制從而抑制蛋白質(zhì)合成。這種結(jié)合并不誘導(dǎo)mRNA靶的降解，就是說作為翻譯抑制子本身不影響對應(yīng)mRNA的豐度，其原因據(jù)推測是由于miRNA和結(jié)合位點之間不完全互補。這就區(qū)別于siRNA的介導(dǎo)的mRNA的降解。但是其他一些miRNAs可能以類似siRNA的方式介導(dǎo)目的RNA的降解。實驗表明引入和let-7目的mRNA靶完全互補的miRNA會誘導(dǎo)mRNA靶的降解。還有實驗結(jié)果表明一些miRNA，包括在植物中發(fā)現(xiàn)的Scarecrow miRNA，能結(jié)合完全互補的mRNA鏈從而降解mRNA序列，抑制蛋白合成。這提示miRNAs可以和siRNAs一樣作用，這兩種小分子RNA作用通路可能有重疊的部分。這種重疊同樣提示siRNAs可能也有和miRNAs同樣的功能。一個很有趣的實驗證實這個觀點：Doench和同事挑選一個已知在體內(nèi)可以有效使CXCR4基因沉默的siRNA，然后在熒光素酶報告基因的3’端插入對應(yīng)的CXCR4結(jié)合位點——其中一個拷貝是插入一個完全匹配的CXCR4結(jié)合位點，另一個拷貝插入4個只有3’和5’端匹配，而中間不同的CXCR4結(jié)合位點，這樣選定的siRNA就不能完全結(jié)合到這個結(jié)合位點——中間形成一個突起的不匹配的環(huán)。將這兩個拷貝轉(zhuǎn)入Hela細胞并用siRNA誘導(dǎo)基因沉默。結(jié)果很有趣——兩個實驗都錄得熒光素酶活性下降了超過10倍，RT-PCR和Northern分析證實，第一個實驗的熒光素酶轉(zhuǎn)錄本下降了超過10倍，這正是正常的siRNA介導(dǎo)的RNAi反應(yīng)，目標(biāo)靶mRNA降解導(dǎo)致表達水平的下降，而第二個實驗中熒光素酶轉(zhuǎn)錄本僅僅下降1.2倍，這種目的基因表達水平下看起來象源于miRNA介導(dǎo)的翻譯抑制降，而不是siRNA介導(dǎo)的影響mRNA的穩(wěn)定性導(dǎo)致。實驗表明：siRNA可能以miRNA的方式作用于mRNA。實驗人員還進行了另一個實驗：改變第二個實驗中的不匹配環(huán)的堿基序列看起來不影響抑制效果，但是siRNA和報告基因上的結(jié)合位點的匹配程度越高抑制效果越好，增加siRNA的量，抑制效果越好——這一點和siRNA抑制的情況一樣——不同的是：完全匹配的結(jié)合位點（siRNA作用方式）可以單獨起作用而相互不影響，而增加不完全配對的結(jié)合位點（注意在第二個實驗中用了4個CXCR4結(jié)合位點）的個數(shù)對翻譯抑制有顯著的加乘作用。在哺乳動物細胞中還沒有找到內(nèi)源的siRNA，外源的siRNA介導(dǎo)的RNAi作用正是一種抵御機制。而miRNAs則廣泛存在于哺乳動物細胞中，從理論上推測可能參與多種調(diào)控作用。這兩種小東西的作用機制和相互關(guān)系的本質(zhì)就顯得更加撲朔迷離。如何在實驗中正確鑒定siRNA和miRNA，甚至是其他的小分子RNA都成為一個值得關(guān)注的問題。待解決問題播報編輯miRNAs在多個物種中廣泛被發(fā)現(xiàn)，而且在進化上高度保守。這些“小玩意兒”留給我們一大堆謎團：miRNA的確切功能是什么？它的目標(biāo)靶是什么？作用機制是什么？也許需要對植物或者線蟲的基因組進行miRNAs突變株的篩選，在果蠅中可以用targeted-disruption缺失miRNA序列。對miRNA突變株伴隨的表型缺失進行研究，有助于解釋miRNAs的功能。正如Phillip Zamore說的：“如果miRNAs在進化的進程中如此高度保守而沒有任何實際功能，那真是大自然拿科研人員開涮——而且是一個殘酷的玩笑”。研究工具播報編輯隨著小分子RNA日益受到研究人員的重視，很多研究小分子RNA的新方法不斷推出。分離由于小分子RNA可能參與分化、發(fā)育、組織生長、脂肪代謝等生理過程，在不同的組織和發(fā)育階段的表達水平有所不同，進一步了解小分子RNA的生物功能需要確定其在各種生物樣品中的表達水平，因而需要一種精確的定量純化方法，從而得到可信的數(shù)據(jù)。現(xiàn)行的RNA純化方法包括有機溶劑抽提+乙醇沉淀，或者是采用更加方便快捷的硅膠膜離心柱的方法來純化RNA。由于硅膠膜離心柱通常只富集較大分子的RNA（200nt以上），小分子RNA往往被淘汰掉，因而不適用于小分子RNA的分離純化。有機溶劑抽提能夠較好的保留小分子RNA，但是后繼的沉淀步驟比較費時費力。mirVana miRNA Isolation Kit是采用玻璃纖維濾膜離心柱(glass fiber filter，GFF)，既能夠有效富集10mer以上的RNA分子，又能夠兼?zhèn)潆x心柱快速離心純化的優(yōu)點，是一個不錯的選擇。對于特別稀有的分子，由于需要分離大量RNA而導(dǎo)致高背景而降低靈敏度，還可以進一步富集10mer到200bp的小分子RNA來提高靈敏度。探針制備方法其實很簡單：只需要準備目的基因的一小段寡核苷酸序列，3’端另外增加8個和T7啟動子互補的堿基，將這段寡核苷酸和T7啟動子引物退火，用Klenow大片斷補齊得到雙鏈的轉(zhuǎn)錄模版，然后用T7 RNA聚合酶、rNTP和標(biāo)記物混合，體外轉(zhuǎn)錄得到標(biāo)記的小分子RNA探針。這種方法可以快速制備各種標(biāo)記（同位素、非放射性標(biāo)記均可）的小于100nt的小分子RNA探針，適用于包括RPAs，Northerns 和原位雜交等各種方法檢測小分子核仁RNA( small nuclear RNA,snRNA)，small interfering RNA (siRNA),，micro RNA (miRNA)和 mRNA。非放射性標(biāo)記的探針還可以用于原位雜交研究miRNA或者mRNA在組織中的分布。檢測由于小分子RNA是一類很小的分子，部分小分子RNA表達水平可能很低，因而需要極為靈敏而定量的分析工具。由于其分子很小，用RT-PCR的方法來定量研究非常困難，多數(shù)研究人員采用Northern Blots——一種技術(shù)復(fù)雜而費力的方法來檢測小分子RNA的存在。傳統(tǒng)的Northern Blot的方法是是用探針檢測固相支持物（膜）上的目標(biāo)分子，由于用探針檢測液相中的目標(biāo)分子遠比檢測固相中的目標(biāo)更為靈敏，生物通在這里為大家推薦一種基于核酶保護分析方法改進的新方法——將同位素標(biāo)記好的小分子RNA探針和待檢測樣品混合雜交，未雜交的RNA和多余的探針用單鏈核酸酶消化，然后使核酸酶失活，并純化雜交的RNA分子，最后通過變性膠電泳放射自顯影檢測結(jié)果。這個基于液相雜交的新方法不但操作簡單而快速，而且靈敏度極高——可以半定量檢測少至10ng總RNA模版中的小分子RNA，或者說，可以檢測attomole (10-18 mol)級別的靶目標(biāo)。靈敏度是Northern Blot的100倍。除此之外，研究人員還可以在同一個樣品中同時檢測多個小分子RNA和長的RNA模版。應(yīng)該說，這個靈活巧妙的設(shè)計可以為從事小分子RNA實驗的研究人員帶來不少方便。總而言之，無論是siRNA, miRNA, snRNA還是其他的小東西，小分子RNA研究的不斷深入將幫助我們揭示更多生命的奧秘。從生物學(xué)機理上來說，miRNA有成為腫瘤標(biāo)志物的優(yōu)勢，它是腫瘤細胞主動分泌的，隨著腫瘤細胞的生成、凋零，miRNA的表達量一直在變化，所以每種miRNA的表達量代表了在某一刻人類體內(nèi)健康或者疾病的信息。 [1]MiRXES在人體這2000多種miRNA中，他們找出了與胃癌高度相關(guān)的12種miRNA，當(dāng)人體中出現(xiàn)胃癌細胞時，這12種miRNA在血液中的濃度會出現(xiàn)異常。 [2]2015年，由朱興奮和覓瑞創(chuàng)始人周礪寒、鄒瑞陽研發(fā)的胃癌早篩試劑盒獲得專利。這項技術(shù)讓miRNA檢測走向了癌癥早篩的臨床應(yīng)用。 [3]功能分析播報編輯MicroRNA功能分析miRNA 的上調(diào)可用于鑒定功能獲得表型；抑制或下調(diào)可以研究功能缺失表型。上調(diào)與下調(diào)的結(jié)合可用于鑒定被特定miRNA 調(diào)節(jié)的基因，以及特定miRNA 參與的細胞進程。主應(yīng)用包括：◇miRNA 靶定位點的鑒定和驗證◇篩選調(diào)節(jié)某個特定基因表達的miRNAs◇篩選影響某個特定細胞進程的miRNAsmiRNA展望播報編輯miRNA在細胞分化，生物發(fā)育及疾病發(fā)生發(fā)展過程中發(fā)揮巨大作用，越來越多的引起研究人員的關(guān)注。隨著對于miRNA作用機理的進一步的深入研究，以及利用最新的例如miRNA芯片等高通量的技術(shù)手段對于miRNA和疾病之間的關(guān)系進行研究，將會使人們對于高等真核生物基因表達調(diào)控的網(wǎng)絡(luò)理解提高到一個新的水平。這也將使miRNA可能成為疾病診斷的新的生物學(xué)標(biāo)記，還可能使得這一分子成為藥靶，或是模擬這一分子進行新藥研發(fā)，這將可能會給人類疾病的治療提供一種新的手段。新手上路成長任務(wù)編輯入門編輯規(guī)則本人編輯我有疑問內(nèi)容質(zhì)疑在線客服官方貼吧意見反饋投訴建議舉報不良信息未通過詞條申訴投訴侵權(quán)信息封禁查詢與解封?2024?Baidu?使用百度前必讀?|?百科協(xié)議?|?隱私政策?|?百度百科合作平臺?|?京ICP證030173號?京公網(wǎng)安備110000020000

miRNA的功能及其作用機制 - 知乎

miRNA的功能及其作用機制 - 知乎首發(fā)于非編碼RNA切換模式寫文章登錄/注冊miRNA的功能及其作用機制Ai科研繪圖-有課?miRNA的功能miRNA的作用機制1、RNA誘導(dǎo)沉默復(fù)合體（RISC）的形成1.2、miRNA誘導(dǎo)的基因沉默模式及其相關(guān)機制miRNA的功能很多研究證明 miRNA是通過參與調(diào)節(jié)其下游基因翻譯過程面發(fā)揮其生物學(xué)功能。比如，Lai等觀察到果蠅miR-2a、miR-2b、miR-6、miR-11、miR-13a及miR-13b等的5'端6~8nt序列具有一定的關(guān)聯(lián)性，它們均可與K框(Kbor)的相同序列互補K框是作為負調(diào)控果蠅增強子斷裂( enhancer split)復(fù)合體基因的3'UTR序列中的保守基因序列。對于一些帶有K、GY或Brd框的基因(GY和Brd框是類似于K框的其他基因3'UTR中的控制元件)，可以被 miRNA識別并與之堿基配對。其實，基于 MIRNA作用機制，可將其分成兩個區(qū)域，其5'端的核苷酸代表了“姓”( family)區(qū)域，該區(qū)域匹配這些框中的一個，而其他的區(qū)域類似“名”( forename)，特異白匹配特定的靶，在動物中，單個mRNA可識別多個mRNA靶標(biāo)，一個mRNA靶標(biāo)可被多個 miRNA識別。根據(jù)miRNA保守的5'端“種子”順序同源性搜索分析，推測人類基因組中約三分之二的蛋白質(zhì)編碼基因受 miRNA的調(diào)控。已知所有動物 miRNA作用的mRNA靶點均在其3＇UTR。miRNA的作用機制 miRNA對靶基因的作用機制一直是眾多研究人員的關(guān)注熱點。最早被發(fā)現(xiàn)的兩個miRNA ——lin4和let-7被認為是通過不完全互補結(jié)合到基因mRNA 3' UTR，以一種未知的方式抑制蛋白質(zhì)翻譯，進而抑制蛋白質(zhì)合成，阻斷mRNA的翻譯過程。后來的研究也發(fā)現(xiàn)，多個果蠅 miRNA和它們的基因mRNA的 3' UTR 存在部分同源。但由于 miRNA與其目標(biāo)靶之間的互補是不完全的，用生物信息學(xué)的方法鑒定 miRNA的目標(biāo)位點并非易事。在植物中，由于 miRNA與潛在的基因是完全互補的，使得植物的miRNA預(yù)測相對較容易。但這些預(yù)測基因是否就是 miRNA的靶基因，還需要作進一步驗證。研究表明， miRNA基因是一類高度保守的基因家族，按其與基因的作用模式不同，主要可分為以下3種類型：①作用時與靶標(biāo)基因完全互補結(jié)合，作用方式和功能與 siRNA非常類似，最后切割mRNA，常見于植物。②作用時與靶標(biāo)基因不完全互補結(jié)合，進而阻止翻譯而不影響mRNA的穩(wěn)定性，這是目前發(fā)現(xiàn)最多的作用模式，常見于動物。(如下圖)（圖一)③具有以上兩種作用模式，當(dāng)與標(biāo)基因完全互補結(jié)合時，直接向切割mRNA，當(dāng)與標(biāo)基因不完全互補結(jié)合時，阻止基因翻譯。（如上圖） miRNA對基因的調(diào)控，正如前文所述(一文讀懂miRNA的生物合成)， Pre-miRNA由 exportin-5輸出至胞漿中，然后釋放 Pre-miRNA. Pre-miRNA與Dicer互補結(jié)合，產(chǎn)生長度為22nt的不完全配對的雙鏈RNA。最后，雙鏈中只有一條單鏈與RNA誘導(dǎo)的RISC結(jié)合，隨后與把mRNA互補。而 miRNA*釋放后則被降解。對于 miRNA來說，發(fā)揮對靶基因的調(diào)控作用， Dicer和RISC是必不可少的。因為 Dicer是產(chǎn)生 miRNA不可或缺的，而RISC則是 miRNA實現(xiàn)功能的載體。1、RNA誘導(dǎo)沉默復(fù)合體（RISC）的形成 2001年， Elbashir等在《基因發(fā)育》雜志( Genes Devolopment)發(fā)表一篇文章，介紹了在果蠅體外系統(tǒng)中加入合成21~23nt的 siRNA，使之能有效降解同源mRNA他們發(fā)現(xiàn)當(dāng)siRNA濃度增加到一定閾值時，mRNA降解程度不再繼續(xù)增加，提示在果蠅裂解液中含有一定數(shù)量RNAi所需蛋白因子。這些RNAi所需蛋白因子是一種復(fù)合物，被定義為RNA誘導(dǎo)的沉默復(fù)合體(RISC）。研究發(fā)現(xiàn)，RISC是一種核糖核蛋白，主要由RNA和蛋白質(zhì)成分組成。其中的RNA即是siRNA，而蛋白質(zhì)成分主要為AGO22、VIG、dFXR以及Dmp68等，并且，這些蛋白質(zhì)成分是組成RISC所必須的，并參與RNAi過程。 miRNA介導(dǎo)的RISC簡稱為 miRISC( miRNA-containing RNA induced silencing coplex)，也被稱作miRNA核糖核蛋白復(fù)合體( miRNP)。miRISC復(fù)合體除了包括成熟 miRNA外，還包含Dicer蛋白和多種其他相關(guān)蛋白。其與RISC結(jié)合的原理與siRNA類似，通過miRNA: miRNA*雙體兩端熱力學(xué)穩(wěn)定性的分析，可以分為兩類結(jié)合：優(yōu)勢結(jié)合與等勢結(jié)合。以 dsRNA為例，當(dāng)雙鏈中兩根支鏈的穩(wěn)定性相似或相同時，它們結(jié)合進入RISC的概率也相似或相同，因此稱為等勢結(jié)合（如圖一所示）。當(dāng)雙鏈中支鏈的穩(wěn)定性相對較弱時，解旋會從穩(wěn)定性弱的一支解開dsRNA，從而會偏向性地產(chǎn)生一條結(jié)合到RISC復(fù)合體上，這類結(jié)合稱為優(yōu)勢結(jié)合，未進入RISC的互補鏈RNA會很快降解(如圖二所示)。(圖二） RISC是 miRNA參與靶基因調(diào)控過程中不可或缺的載體。在 miRISC復(fù)合體中， Dicer對Pre-miRNA的處理與雙鏈螺旋的解旋是偶聯(lián)進行的。通常，只有一條鏈進入 miRISC，具體選擇雙鏈中哪一條鏈取決于堿基熱動力學(xué)穩(wěn)定性等因素。不進入RISC的 miRNA鏈被稱之為伴隨鏈( passenger)，并被冠以星號(*)，具有更低的穩(wěn)定性，通常情況下被降解掉。但在某些情況下，兩條鏈均具有活性，成為針對不同靶基因mRNA的功能 miRNA。RISC是具有多輪催化效應(yīng)的酶。在這一過程中，其核心組分Ago2發(fā)揮重要作用。因此，在組成 miRISC的蛋白質(zhì)中，Ago蛋白家族成員在RISC功能中處于中心地位，Ago蛋白家族在哺乳動物中有8種，分為Ago和PIWI兩個亞家族。人Ago亞家族有四種: hagol-4；PIW亞家族有HIWI、HILI、 PIWIL3、HIWI2四種。果蠅有兩種Ago蛋白，分別是Agol和Ago2。(圖三） Ago家族蛋白為一類分子質(zhì)量約為100kD的蛋白質(zhì)，屬于進化保守的家族，包含有PAZ和Piwi兩個保守的RNA結(jié)合結(jié)構(gòu)域，是目前唯一一種在所有RNAi和 miRNA通路中均可發(fā)現(xiàn)的蛋白。PAZ結(jié)構(gòu)域負責(zé)結(jié)合引導(dǎo)鏈( guide) miRNA的3' 端突出的2個核苷酸或者單鏈RNA的3'-OH；PIWI結(jié)構(gòu)域則負責(zé)組裝核酶H( ribonuclease- H)，并與 miRNA 5＇端結(jié)合。Ago蛋白與 miRNA結(jié)合使其朝向正確，以便與靶基因mRNA作用。Ago蛋白可能招募其他蛋白行使翻譯抑制功能;一些Ago蛋白直接切割靶轉(zhuǎn)錄本。（如圖三所示） Ago家族有不同的突變種和表型。研究發(fā)現(xiàn)，秀麗線蟲有24個Ago蛋白，果蠅中有5個Ago蛋白，乳動物有8個同源蛋白Ago蛋白，所以RISC會呈現(xiàn)不同類型或者調(diào)控方式。根據(jù)Ago的不同，可以將RISC分為切割RISC與非切割RISC兩類。對于一個特定的RISC是否切割一個mRNA分子，主要取決于以下幾個方面：目標(biāo)mRNA的特性(主要包括分子結(jié)構(gòu)及數(shù)量等)；RISC的類型必須為切割RISC；組織中，RISC的切割速度；miRNA與靶基因必須滿足一定的匹配程度；miRNA的來源。在人基因組中含有的8個AgO蛋白中，有4個成員存在于所有乳動物細胞中，在人類這類蛋白稱為E1F2C/ hAgo；PIWI存在于精細胞和細胞中，RISC的其他組成分還包括人類免疫缺陷病毒活化反應(yīng)RNA結(jié)合蛋( human immunodeficiency virus tran activating response RNA binding protein，TRBP)，干擾素誘導(dǎo)的蛋白激酶活化因子(wro rein activator of the interferon induced protein kinase，PACT)，運動神經(jīng)元存活復(fù)合體( survival of motor neurons complex)，脆性X智障蛋白( fragile X mental retardation protin，F(xiàn)MRP)和 Tudor葡萄球菌核酸酶結(jié)構(gòu)域包含蛋白( Tudor staphylococcal nuclease domain contining protein) 等。RISC的結(jié)構(gòu)特征主要包含以下幾個方面：(1)成熟的 miRNA與RISC結(jié)合。RISC含Dicr及其他蛋白質(zhì)。RISC又稱 miRNP，和 miRNA結(jié)合的RISC稱為“ miRISC"。(2) Dicer 加工pre-miRNA與RNA雙鏈解旋偶聯(lián)，解旋的 miRNA只有一條單鏈保留在RISC中。(3) argonaute(Ago)是RISC的核心成分，為 miRNA誘導(dǎo)的基因沉默所必需。Ago含有兩個RNA結(jié)合域：PAZ，與成熟 MIRNA的3' 端結(jié)合；PIWI，類似核糖核酸酶-H，和引導(dǎo)鏈5'端結(jié)合。兩者共同將成熟 miRNA定向，使其和靶mRNA互補。（如圖四所示）（圖2、miRNA誘導(dǎo)的基因沉默模式及其相關(guān)機制 miRNA靶向互補 mRNAs導(dǎo)致目的mRNA切降解的過程被稱為轉(zhuǎn)錄后基因沉默(ot ranscriptional gene silencing，PTGS)。有效的PTGS需要RISC對mRNA轉(zhuǎn)錄本的切割。 miRNA可以指導(dǎo)RISC在轉(zhuǎn)錄后水平下調(diào)基因的表達——mRNA的降解或翻譯抑制。采取何種沉默方式是由mRNA的特性所決定的。如果mRNA能夠與miRNA完全互補，該mRNA就會被RISC特異地降解；如果mRNA不能與 miRNA完全互補，僅在某個位點與 miRNA互補，那么RISC就不會特異地降解mRNA，只是阻止mRNA作為翻譯的模板，使之不能合成蛋白質(zhì)。在動物中，多數(shù)情況下復(fù)合物中的單鏈 miRNA與mRNA的 3' UTR不完全互補配對，從而阻礙對該mRNA的翻譯，并以此來調(diào)控基因表達，但不影響mRNA的穩(wěn)定性。如線蟲中的 miRNA lin-4就是以這種方式調(diào)控它的兩個靶基因——lin-14和lin-28的翻譯。另一種主要的作用方式則與 siRNA誘導(dǎo)的轉(zhuǎn)錄后基因沉默的PTGS相類似，當(dāng) miRNA與mRNA完全互補配對時，Ago2蛋白可通過對mRNA的切割直接導(dǎo)致其降解，完成基因沉默調(diào)控。此外， miRNA誘導(dǎo)的基因沉默還存在一些其他的方式，如 miRNA還能通過組氨酸修飾和啟動子區(qū)的DNA甲基化影響基因的表達；miRNA與 5' UTR相互作用然后上調(diào)基因表達，由胞漿轉(zhuǎn)運入核，以及近些年來發(fā)現(xiàn)的 miRNA能加速mRNA脫腺苷酸化( accelerated deadenylation)而抑制基因表達等多種作用模式。miRNA誘導(dǎo)基因沉默的機制可以歸納為以下兩個主要方面:(1) miRNA的翻譯起始抑制與翻譯起始后抑制 miRNA對翻譯起始抑制的相關(guān)機制主要有如下一些觀點：首先， miRNA可通過抑制核糖體的組裝來阻斷翻譯起始，進而起到對翻譯過程的抑制作用。miRNA的抑制作用需要靶mRNA具有m7G帽子結(jié)構(gòu)成為支持這一理論的重要依據(jù)，由此可以推斷 miRISC可能通過對翻譯起始復(fù)合物形成抑制而發(fā)揮作用；Ago2中間結(jié)構(gòu)域具有結(jié)合m7G帽子的活性，Ago2通過對miRNA招募靶mRNA的 3' UTR，從而與起始復(fù)合物eIF4E/G競爭性結(jié)合m7G帽子，最終發(fā)揮對翻譯起始復(fù)合物的抑制作用。還有一些觀點認為，通過影響靶mRNA脫腺嘌呤反應(yīng)，導(dǎo)致其 polyA尾縮短，從而使mRNA與 polyA結(jié)合蛋白( polya binding protein，PABP)受阻，進而影響蛋白質(zhì)翻譯的起始。研究還表明，一些被 miRNA作用后的mRNA可以與多核糖體偶聯(lián)，這些核糖體在翻譯中處于非常活躍的狀態(tài)。此外， miRNA的抑制作用還可能發(fā)生在翻譯起始之后，這主要是由于其翻譯過程的抑制作用是通過內(nèi)部核糖體進入位點( internal ribosome entry site，IRES)什么是IRES，而不是依賴 MRNA m7G帽子來發(fā)揮作用。其他作用方式，比如對新生多肽鏈的翻譯同步降解等目前還沒有定論，有待進一步證實。(2) miRNA介導(dǎo)的mRNA衰減(降解) miRNA可誘導(dǎo)與其不完全配對的犯mRNA衰減(降解)。通過Ago蛋白定位于如P小體( processing bodies，P- bodies)等的RNA顆粒( RNA granules)中，這些顆粒中包含有mRNA降解的酶。這也可能是 miRNA介導(dǎo)mRNA衰減的一個重要途徑。發(fā)布于 2021-09-04 23:51miRNA分子生物學(xué)基因組?贊同 147??7 條評論?分享?喜歡?收藏?申請轉(zhuǎn)載?文章被以下專欄收錄非編碼

一文秒懂microRNA - 知乎

一文秒懂microRNA - 知乎首發(fā)于解螺旋切換模式寫文章登錄/注冊一文秒懂microRNA酸菜?科研等 2 個話題下的優(yōu)秀答主本文首發(fā)于“解螺旋”微信公眾號轉(zhuǎn)載請注明：解螺旋·臨床醫(yī)生科研成長平臺酸菜今天可是有點大跌眼鏡，以科普著稱的某殼網(wǎng)竟然也聊起了“micro RNA”,這一只在生物學(xué)界才被熟知的名詞，已經(jīng)“熱”到日常生活了么？老貓同志說的沒錯，雖然科學(xué)家們發(fā)現(xiàn)了很多microRNA與某些重要的生理、生化進程或疾病直接相關(guān)，但是大部分的應(yīng)用目前還停留在實驗室或者初級臨床的層級里。畢竟microRNA的研究至今只有20多年的歷史，人類對于它的了解還不成熟。就連這個科班出身的，上學(xué)時也只知道m(xù)RNA，tRNA和rRNA，做了科研后才知道，原來還有MiRNA、SiRNA、LncRNA、PiwiRNA、CeRNA……不過，如果你是醫(yī)院的小伙伴們，如果還沒有搞懂MicroRNA，那你可就真的要OUT了。酸菜今天興致來了，也來為MicroRNA科普一把！絕壁比某網(wǎng)接地氣的，有木有？MicroRNA (miRNA) 是一類由內(nèi)源基因編碼的長度約為22 nt的非編碼單鏈RNA 分子,它們在動植物中參與轉(zhuǎn)錄后基因表達調(diào)控。過于教條，過于高大上？往簡單地講，Micro RNA就是一條不會翻譯蛋白的小RNA。為什么是22nt，而不是22bp？（nt是核苷酸，bp是堿基對）Micro RNA是用nt作為單位的，說明了miRNA是單鏈的。我們在文獻里miRNA名字有沒有覺得很奇怪？有has、3p、5p，有的后面還帶*號，還有的有a有b，有的a、b后面跟個-1、-2……完全看不懂有沒有？我來給大家解讀一下，如下圖。miRNA就是一條不會翻譯蛋白的小RNA，那么miRNA對人體到底有什么作用？給你舉個例子，你感受一下。普通的mRNA就好比是一條高速公路，路上會有很多會排出尾氣的汽車（核糖體，它們在mRNA上邊走邊翻譯蛋白），一條高速路上會有很多輛車（多聚核糖體Polysome），車越多、開得越快，尾氣就越大（蛋白表達量就越高），這個時候，在路快到盡頭的地方（mRNA的3’UTR上）就出現(xiàn)了一個交警（MiRNA聚合一些蛋白的RISC，RNA-Induced SilencingComplex，RNA誘導(dǎo)沉默復(fù)合體），他穩(wěn)穩(wěn)地站在路的最后（通過RISC中的MiRNA與3’UTR互補，結(jié)合到mRNA的3’UTR上），整個車隊就停下來了，尾氣也沒了（蛋白表達降低）。好了，現(xiàn)在也明白為什么過表達miRNA之后下游基因的mRNA變化不大，但蛋白會有變化了吧？因為警察是不會拆路的……發(fā)布于 2017-12-12 13:00核糖核酸（RNA）基因科研?贊同 165??10 條評論?分享?喜歡?收藏?申請轉(zhuǎn)載?文章被以下專欄收錄解螺旋關(guān)于醫(yī)學(xué)科研的獨到

醫(yī)學(xué)前沿：非編碼RNA—microRNA - 知乎

醫(yī)學(xué)前沿：非編碼RNA—microRNA - 知乎首發(fā)于基因研究發(fā)展史切換模式寫文章登錄/注冊醫(yī)學(xué)前沿：非編碼RNA—microRNA啟領(lǐng)生物在2019年國家自然科學(xué)基金資助項目中，以非編碼RNA為研究主線的miRNA/IncRNA/CircRNA/CeRNA占中標(biāo)總數(shù)的5成以上！▲RNA項目中標(biāo)數(shù)近幾年，涉及到RNA的項目數(shù)連年呈上升趨勢，絲毫沒有“減熱”。預(yù)計2020年，中標(biāo)項目在保持現(xiàn)有的基礎(chǔ)上依舊有上升的可能。今天我們主要講的是是非編碼RNA中“老而彌堅”的熱點—microRNA(miRNA)。注：2019年，涉及到miRNA研究的中標(biāo)項目至少為210項，熱度已維持多年，位居國自然申請熱點榜的“榜首”。隨著研究的不斷深入，單個miRNA已很難滿足評審組，其漸漸淪為工具分子或需多個miRNA“抱團取暖”才可以?！鴼v年自然科學(xué)基金-miRNA中標(biāo)項目數(shù)下面小編將帶大家深度“扒一扒”miRNA，從概念、生成過程、生物學(xué)功能、在生物醫(yī)學(xué)領(lǐng)域的應(yīng)用和miRNA實驗設(shè)計思路進行深入介紹。希望可以為大家的項目申請和實驗設(shè)計提供新的思路。在遺傳學(xué)中，微RNA（microRNAs，miRNA）是一類進化上保守的非編碼小分子RNA，長度一般在21-23個核苷酸之間，具有在翻譯水平調(diào)控基因表達的功能。在脊椎動物基因組中有多達1000個不同的miRNA，調(diào)控至少30%以上的基因表達。miRNA廣泛存在于多種真核生物中，其生物學(xué)特征主要表現(xiàn)為：①高度保守性：miRNA保守性具有重要的生物學(xué)意義，提示在不同生物發(fā)育過程中，miRNAs具有相同的調(diào)控機制。②時序表達特異性性：在不同組織、不同發(fā)育階段，miRNA的表達水平有顯著差異，miRNA表達是動態(tài)調(diào)控的。③組織表達特異性：一些miRNA表達具有細胞和組織特異性。▲miRNA的形成在細胞核內(nèi)，基因組DNA轉(zhuǎn)錄生成較長的RNA分子（長度達1000nt），其被雙鏈RNA特異性的核糖核酸酶Drosha切割成長度大約70-100堿基的具有發(fā)夾結(jié)構(gòu)的RNA分子（primary transcripts，pri-miRNA）。這些具有發(fā)夾結(jié)構(gòu)的RNA分子經(jīng)核輸出蛋白exportin5機制轉(zhuǎn)運到細胞質(zhì)，然后被第二個雙鏈RNA特異的核糖核酸酶Dicer切割，形成19-23nt大小的成熟的miRNAs?！鴐iRNA形成和行使功能示意圖成熟的單鏈miRNAs與類似RNA誘導(dǎo)沉默復(fù)合物（RISC）結(jié)合，并參與RNA干擾反應(yīng)（RNAi）。在動物中，結(jié)合在復(fù)合物上的miRNA以一種目前尚未完全清楚的機制結(jié)合到基序基本互補的mRNA上，但這種結(jié)合并不像RNAI反應(yīng)那樣參與mRNA降解，而是阻止所結(jié)合的mRNA的翻譯，導(dǎo)致相應(yīng)基因表達水平的降低?！鴐iRNA功能示意圖▲蛋白功能受到多個miRNA分子的調(diào)控最新的研究表明，miRNA除了經(jīng)典的下調(diào)基因的表達之外，還有7種非經(jīng)典調(diào)控分子機制。①Pri-miRNA可被翻譯為多肽：pri-miRNA進入胞質(zhì)中被核糖體識別為mRNA，翻譯為多肽行使生理功能。②miRNA與功能蛋白結(jié)合：miRNA與AGO蛋白復(fù)合物組成RISC，靶向降解mRNA外，還可與其他功能性蛋白結(jié)合，發(fā)揮非經(jīng)典調(diào)控途徑。③直接激活TLR受體蛋白。④提高蛋白表達水平。⑤miRNA靶向調(diào)控線粒體相關(guān)基因mRNA：該類miRNA一般都具有同時調(diào)控多個線粒體相關(guān)基因的mRNA；⑥直接激活基因轉(zhuǎn)錄過程：如miR-589復(fù)合物可結(jié)合cyclooxygenase-2 (COX2)啟動子區(qū)序列，啟動該基因的轉(zhuǎn)錄過程。⑦靶向負調(diào)控其他非編碼RNA的前體RNA：在細胞核內(nèi)，miRNA可靶向降解了pri-miRNA。▲miRNA經(jīng)典作用機制▲miRNA非經(jīng)典調(diào)控機制匯總（圖片源自《cell》）miRNA的功能涉及到各種生理病理過程，包括：發(fā)育過程調(diào)節(jié)、抵抗病毒入侵、動物免疫功能調(diào)節(jié)、各器官/系統(tǒng)疾病以及腫瘤?！鴐iRNA對神經(jīng)元發(fā)育的影響▲miRNA與腫瘤▲miRNA對血小板功能的影響1、尋找研究對象：首先精確的了解課題是針對哪種疾病中的哪個通路、哪個蛋白，再尋找感興趣的miRNA或蛋白作為研究對象，如在樣本中異常升高或降低的指標(biāo)。2、確認研究對象：廣泛檢索資料，經(jīng)多種方法分析高通量數(shù)據(jù)，確定目的miRNA或蛋白在目的樣本中升高或降低。該步驟是后續(xù)實驗的基礎(chǔ)，必須重視。3、尋找靶關(guān)系：應(yīng)用在線的預(yù)測平臺或生物信息學(xué)技術(shù)尋找目的miRNA可能與哪些蛋白存在相互關(guān)系，或者目的蛋白可能是哪些miRNA的靶蛋白。感興趣的可參考該網(wǎng)址提供的方法：http://weixin.shengxin.ren/web/wei_xin/examples/Html/290000/296256.html；https://blog.csdn.net/herokoking/article/details/77863126。4、確認靶關(guān)系：確認在體內(nèi)這種靶關(guān)系確實存在，miRNA會降低靶蛋白的表達量。5、確認生物功能：證明miRNA-靶蛋白這種相互作用會導(dǎo)致生物學(xué)功能改變。功能實驗的量、涉及范圍、技術(shù)手段及重要程度是文章意義和影響因子的決定因素。▲miRNA實驗設(shè)計思路https://mp.weixin.qq.com/s/hiHHrBvS0P0rcPvF-_PlKw發(fā)布于 2020-06-30 12:33非編碼RNAmiRNA核糖核酸（RNA）?贊同 73??4 條評論?分享?喜歡?收藏?申請轉(zhuǎn)載?文章被以下專欄收錄基因研究發(fā)展史基因科技什么時候可以改變

微RNA_百度百科

_百度百科網(wǎng)頁新聞貼吧知道網(wǎng)盤圖片視頻地圖文庫資訊采購百科百度首頁登錄注冊進入詞條全站搜索幫助首頁秒懂百科特色百科知識專題加入百科百科團隊權(quán)威合作下載百科APP個人中心收藏查看我的收藏0有用+10微RNA播報討論上傳視頻真核生物中的RNA分子微RNA（microRNAs；miRNA，又譯小分子RNA）是真核生物中廣泛存在的一種長約21到23個核苷酸的RNA分子，可調(diào)節(jié)其他基因的表達。miRNA來自一些從DNA轉(zhuǎn)錄而來，但無法進一步轉(zhuǎn)譯成蛋白質(zhì)的RNA（屬于非編碼RNA）。miRNA通過與靶信使核糖核酸(mRNA)特異結(jié)合，從而抑制轉(zhuǎn)錄后基因表達, 在調(diào)控基因表達、細胞周期、生物體發(fā)育時序等方面起重要作用。在動物中，一個微RNA通?？梢哉{(diào)控數(shù)十個基因。這些RNA是從初級轉(zhuǎn)錄本（primary transcript），也就是pri-miRNA，轉(zhuǎn)變成為稱為pre-miRNA的莖環(huán)結(jié)構(gòu)，最后成為具有功能的miRNA。中文名微RNA外文名microRNAs別????名又譯小分子RNA解????釋內(nèi)生的長度約20-24個核苷酸小RNA所屬分類真核生物目錄1簡介2微RNA的作用簡介播報編輯微RNAMicroRNA（miRNA）是一類內(nèi)生的、長度約20-24個核苷酸的小RNA，其在細胞內(nèi)具有多種重要的調(diào)節(jié)作用。每個miRNA可以有多個靶基因，而幾個miRNAs也可以調(diào)節(jié)同一個基因。這種復(fù)雜的調(diào)節(jié)網(wǎng)絡(luò)既可以通過一個miRNA來調(diào)控多個基因的表達，也可以通過幾個miRNAs的組合來精細調(diào)控某個基因的表達。據(jù)推測，miRNA調(diào)節(jié)著人類三分之一的基因。MicroRNA存在多種形式，最原始的是pri-miRNA，長度大約為300~1000個堿基；pri-miRNA經(jīng)過一次加工后，成為pre-miRNA即microRNA前體，長度大約為70~90個堿基；pre-miRNA再經(jīng)過Dicer酶酶切后，成為長約20~24nt的成熟miRNA。實際研究中，pre-miRNA應(yīng)用最早，也最廣泛，很多商業(yè)化的MicroRNA庫都是pre-miRNA形式的。近幾年來，研究發(fā)現(xiàn)microRNA的雙臂對成熟miRNA的形成有著十分重要的作用，所以天然的pri-miRNA形式越來越多地被研究者采用。 [1]miRNA的二級結(jié)構(gòu)為A型雙螺旋。1989年，Victor發(fā)現(xiàn)線蟲 ( C. elegans) 中有個基因 lin-4 抑制另一個基因 lin-14. 他們認為 lin-4 應(yīng)該也表達一種調(diào)控蛋白質(zhì)，因為基因轉(zhuǎn)錄成RNA并翻譯成蛋白質(zhì)是當(dāng)時認為的公理。1993年，Victor的學(xué)生 Rosalind Lee 和 Phonda Feinbaum 克隆出了 lin-4，卻發(fā)現(xiàn)這個基因非常小，而且這個基因的產(chǎn)物不是蛋白質(zhì)，而是一個長度只有22個核苷酸的RNA。它是由單鏈的RNA分子產(chǎn)生，這個分子的一端折回來形成不完全的互補配對，稱"發(fā)卡結(jié)構(gòu)".與小分子siRNAs相比，miRNA在分子特性等方面是相似的，但也存在不少的差異。siRNA是雙鏈RNA，3‘端有2個非配對堿基，通常為UU； miRNA是單鏈RNA。 siRNAs是由dsDNA在Dicer酶切割下產(chǎn)生，而成熟miRNAs的產(chǎn)生要復(fù)雜一些，首先pri-miRNA在核內(nèi)由一種稱為Drosha酶處理后成為大約70nt的帶有莖環(huán)結(jié)構(gòu)的Precursor miRNAs (pre-miRNAs), 這些pre-miRNAs再在Exportin-5幫助下轉(zhuǎn)運到細胞核外之后再由胞質(zhì)Dicer酶進行處理，酶切后成為成熟的miRNAs。生命的一些重要活動如幼蟲的生長發(fā)育、細胞的發(fā)生和分化、神經(jīng)系統(tǒng)的分化等都被一些非編碼蛋白的小RNA的調(diào)控, 而除miRNA、siRNA以外的小RNA我們知之甚少。微RNA的作用播報編輯人類基因組計劃結(jié)束后，人們發(fā)現(xiàn)編碼蛋白質(zhì)的基因只占總基因組的約2%。而占人類基因組95%的非編碼序列竟是產(chǎn)生大量非編碼RNA的源泉，這些非編碼RNA主要充當(dāng)調(diào)控者的角色，在細胞分化凋亡、生物發(fā)育、疾病發(fā)生等方面均起重要作用。其實，RNA比DNA更為古老，它組成了地球上最早的生命。生命起源初期，沒有由核酸編碼的蛋白，生命體由RNA組成，這被稱為“RNA世界”。RNA既攜帶遺傳信息，又承擔(dān)催化分子的作用，參與自身復(fù)制。雖然后來出現(xiàn)了DNA，但RNA依舊承擔(dān)著很多調(diào)控功能。在線蟲中發(fā)現(xiàn)的一種微小RNA（miRNA）——let-7 RNA，就是RNA調(diào)控生物發(fā)育的一個突出代表。它在線蟲幼蟲的3/4期出現(xiàn)，它一出現(xiàn)便會抑制Lin-41等蛋白的表達，同時解除對Lin-29蛋白表達的抑制，使線蟲進入成蟲期。一旦它的一個堿基發(fā)生突變，就可使線蟲永遠停留在幼蟲期，而無法成熟。另一個代表是費厄和麥洛發(fā)現(xiàn)的雙鏈RNA能引發(fā)RNA干擾——他們兩人因此獲得2006年諾貝爾醫(yī)學(xué)獎。小分子調(diào)控RNA已成為分子生物學(xué)中的熱點和前沿。因為，小干擾RNA在細胞質(zhì)中調(diào)控蛋白質(zhì)的生物合成，在細胞核內(nèi)引發(fā)DNA的甲基化，進而引發(fā)表觀遺傳學(xué)的一系列變化，可謂“重權(quán)在握”。除此以外，一些微RNA還可以激活心肌細胞的再生能力。在我們出生后不久，心臟就喪失了再生能力。所以，當(dāng)心臟病發(fā)作時，心肌細胞死亡，受損心肌并未長出新生的心肌細胞，而是被瘢痕組織替代。如今，意大利德里亞斯特國際遺傳工程和生物技術(shù)中心的莫羅·賈克（Mauro Giacca）及其同事們，已經(jīng)鑒定出了能夠激活成年人心肌細胞分裂增殖的分子。之后，他們將在真正的生命體上利用這些分子，誘導(dǎo)心肌細胞分裂增殖。此項工作燃起了我們讓受損心臟重獲新生的希望。為了弄清楚哪些微RNA參與心肌細胞的分裂，賈克的團隊在人工培養(yǎng)的嚙齒動物心肌細胞中測試了875個人類微RNA。他們發(fā)現(xiàn)有204個微RNA可以再度激活細胞增殖，其中兩個能夠影響近2000個基因。賈克認為，只要微RNA不會引起其他細胞的增殖，比如造成腫瘤之類的，對心臟病突發(fā)人群來說，這一方法將會成為一項很有價值的介入治療法。 [2]但RNA調(diào)控功能不僅限于小分子RNA，大型RNA調(diào)控本領(lǐng)也不示弱。女性細胞中有一種長達一萬核苷酸的XistRNA，最終能使女性一條染色體被關(guān)閉，使男女性X染色體編碼基因的表達量相同。調(diào)控RNA擁有龐大的家族，至今已知的就有小閱讀框RNA、印記RNA、微衛(wèi)星RNA、反向轉(zhuǎn)錄RNA、反轉(zhuǎn)座子RNA等等，還有更多種類有待科學(xué)家發(fā)現(xiàn)。自2005年以來，我國已有五個與RNA有關(guān)的國家重大項目。我國科學(xué)家在腫瘤、心血管病等領(lǐng)域，也已取得一些好的成績。世界各國已有多種核酸技術(shù)進入生物產(chǎn)業(yè)，過百種的各類核酸藥物進入臨床試驗。 [3]從生物學(xué)機理上來說，miRNA有成為腫瘤標(biāo)志物的優(yōu)勢，它是腫瘤細胞主動分泌的，隨著腫瘤細胞的生成、凋零，miRNA的表達量一直在變化，所以每種miRNA的表達量代表了在某一刻人類體內(nèi)健康或者疾病的信息。 [4]MiRXES在人體這2000多種miRNA中，他們找出了與胃癌高度相關(guān)的12種miRNA，當(dāng)人體中出現(xiàn)胃癌細胞時，這12種miRNA在血液中的濃度會出現(xiàn)異常。 [5]新手上路成長任務(wù)編輯入門編輯規(guī)則本人編輯我有疑問內(nèi)容質(zhì)疑在線客服官方貼吧意見反饋投訴建議舉報不良信息未通過詞條申訴投訴侵權(quán)信息封禁查詢與解封?2024?Baidu?使用百度前必讀?|?百科協(xié)議?|?隱私政策?|?百度百科合作平臺?|?京ICP證030173號?京公網(wǎng)安備110000020000

microRNAs in action: biogenesis, function and regulation | Nature Reviews Genetics

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Review Article

Published: 28 June 2023

microRNAs in action: biogenesis, function and regulation

Renfu Shang1, Seungjae Lee?

ORCID: orcid.org/0000-0001-5626-96561, Gayan Senavirathne1 & …Eric C. Lai?

ORCID: orcid.org/0000-0002-8432-58511?Show authors

Nature Reviews Genetics

volume?24,?pages 816–833 (2023)Cite this article

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RNAiStructural biology

AbstractEver since microRNAs (miRNAs) were first recognized as an extensive gene family >20?years ago, a broad community of researchers was drawn to investigate the universe of small regulatory RNAs. Although core features of miRNA biogenesis and function were revealed early on, recent years continue to uncover fundamental information on the structural and molecular dynamics of core miRNA machinery, how miRNA substrates and targets are selected from the transcriptome, new avenues for multilevel regulation of miRNA biogenesis and mechanisms for miRNA turnover. Many of these latest insights were enabled by recent technological advances, including massively parallel assays, cryogenic electron microscopy, single-molecule imaging and CRISPR–Cas9 screening. Here, we summarize the current understanding of miRNA biogenesis, function and regulation, and outline challenges to address in the future.

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Fig. 1: Canonical and non-canonical miRNA biogenesis pathways.Fig. 2: Structural and sequence features of miRNA substrates and targets.Fig. 3: Cryo-EM and single-molecule studies of Microprocessor and Dicer complexes.Fig. 4: Strategies for the regulation of miRNA biogenesis.Fig. 5: Regulation of miRNA turnover.

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Download referencesAcknowledgementsThe authors thank G. La Rocca, B. Kleaveland and L. Joshua-Tor for critical reading, and the referees for informative comments. S.L. was supported by a training award from the NYSTEM contract #C32559GG and the Center for Stem Cell Biology at MSK. Work in E.C.L.’s group was supported by the National Institutes of Health (NIH) (R01-GM083300) and MSK Core Grant P30-CA008748. The authors apologize to those whose work is not included owing to space constraints.Author informationAuthors and AffiliationsDevelopmental Biology Program, Sloan Kettering Institute, New York, NY, USARenfu Shang,?Seungjae Lee,?Gayan Senavirathne?&?Eric C. LaiAuthorsRenfu ShangView author publicationsYou can also search for this author in

PubMed?Google ScholarSeungjae LeeView author publicationsYou can also search for this author in

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PubMed?Google ScholarContributionsR.S., S.L., G.S. and E.C.L. wrote and edited the manuscript. R.S. S.L. and G.S. drafted the figures. R.S., S.L., G.S. and E.C.L. discussed and reviewed the manuscript before submission.Corresponding authorCorrespondence to

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Nature Reviews Genetics thanks Shuo Gu, Tuan Anh Nguyen, Ian Macrae who co-reviewed with Luca Gebert, and the other, anonymous, reviewer for their contribution to the peer review of this work.

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微小核糖核酸_百度百科

核酸_百度百科網(wǎng)頁新聞貼吧知道網(wǎng)盤圖片視頻地圖文庫資訊采購百科百度首頁登錄注冊進入詞條全站搜索幫助首頁秒懂百科特色百科知識專題加入百科百科團隊權(quán)威合作下載百科APP個人中心微小核糖核酸播報討論上傳視頻醫(yī)學(xué)術(shù)語收藏查看我的收藏0有用+10MicroRNA是長約22nt的非編碼RNA，廣泛存在于從病毒到人類的各種生物中。這些小RNA能夠與mRNA結(jié)合阻斷蛋白編碼基因的表達，防止它們翻譯成為蛋白?？茖W(xué)家們發(fā)現(xiàn)，microRNA與結(jié)直腸癌等腸道疾病關(guān)系密切，而且能進入線粒體控制其基因表達。中文名微小核糖核酸披????露四個方面的重要信息包????含食物中的任何核酸、蛋白質(zhì)通????過母嬰傳播和通過肉食間接傳遞特????點1.長度一般為20~25個堿基2不同生物體內(nèi)普遍存在目錄1研究2跨物種謀殺3機制研究研究播報編輯披露了四個方面的重要信息：一是“食物中的任何核酸、蛋白質(zhì)，在消化系統(tǒng)中都會被完全消化成核苷酸、氨基酸后被吸收”的觀點被推翻了；二是有數(shù)據(jù)表明，微小核糖核酸非常穩(wěn)定，不容易降解，能順利進入血液，并長期滯留，發(fā)揮調(diào)控作用。并且能夠通過母嬰傳播和通過肉食間接傳遞；三是已經(jīng)發(fā)現(xiàn)了3000多個miRNA，其中大部分在動物體內(nèi)起著關(guān)鍵性的調(diào)控作用，是最主要的基因表達調(diào)控因子之一。估計人體內(nèi)大約2/3的基因都受到某個或一組miRNA的調(diào)控；四是miR-21是著名的原癌miRNA，幾乎所有的癌癥都有它參與。還有一些miRNA調(diào)控著胚胎和嬰兒的發(fā)育，包括骨骼肌肉大腦心臟等幾乎所有的臟器的發(fā)育。如果它們從食物進入人體發(fā)揮作用，就會導(dǎo)致產(chǎn)生畸形、人口素質(zhì)（大腦智力等）異常（倒不一定是下降......）等現(xiàn)象。microRNA研究表明：轉(zhuǎn)基因食品的風(fēng)險還是存在的此前，在生物化學(xué)上所有人都一致認為：食物中的任何核酸、蛋白質(zhì)，在消化系統(tǒng)中都會被完全消化成核苷酸、氨基酸，然后吸收到身體內(nèi)，按照自身需求重新"組裝"成自己的核酸和蛋白質(zhì)。即使是以原型吸收的核酸和蛋白質(zhì)也會被小腸上皮細胞和肝細胞降解，對于消化系統(tǒng)正常的人來說任何原始形態(tài)的核酸和蛋白質(zhì)序列都不可能存在于到體內(nèi)門靜脈以外的血液中，更不可能發(fā)揮調(diào)控作用。然而，從最近的研究結(jié)果來看，這句話被推翻了。首先簡要介紹一下微小核糖核酸。微小核糖核酸MicroRNA（miRNA）是一種小的內(nèi)源性非編碼RNA分子，大約由21－25個核苷酸組成。這些小的miRNA通常靶向一個或者多個mRNA，通過翻譯水平的抑制或斷裂靶標(biāo)mRNAs而調(diào)節(jié)基因的表達。1993年，Lee，F(xiàn)einbaum和Ambros等人發(fā)現(xiàn)在線蟲體內(nèi)存在一種RNA（lin-4），是一種不編碼蛋白但可以生成一對小的RNA轉(zhuǎn)錄本，每一個轉(zhuǎn)錄本能在翻譯水平通過抑制一種核蛋白lin-14的表達而調(diào)節(jié)了線蟲的幼蟲發(fā)育進程。對于出現(xiàn)這種現(xiàn)象的原因，科學(xué)家們猜測是由于基因lin-14的mRNA的3'UTR區(qū)獨特的重復(fù)序列和lin-4之間有部分的序列互補造成的。在第一幼蟲階段的末期降低lin-14的表達將啟動發(fā)育進程進入第二幼蟲階段。7年后科學(xué)家又發(fā)現(xiàn)了第二個miRNA－let-7，let-7相似于lin-4，同樣可以調(diào)節(jié)線蟲的發(fā)育進程。miRNA是十分特殊的RNA，序列非常短，只有22nt，但是有著超常的穩(wěn)定性：在RNA酶中，一般RNA一小時候消化得干干凈凈沒有任何殘余，而miRNA在跟RNA酶混合后保溫水解24小時竟然還保留近一半！后來，至今為止已經(jīng)發(fā)現(xiàn)了3000多個miRNA，其中大部分在動物體內(nèi)都起著關(guān)鍵性的調(diào)控作用，是最主要的基因表達調(diào)控因子之一，據(jù)估計人體內(nèi)大約2/3的基因都受到某個或一組miRNA的調(diào)控。我研究的對象就是一個miRNA，它當(dāng)然有著自己的名字，但是因為結(jié)果尚未發(fā)表，這一微小核糖核酸暫以miR-A代替。已知的是：這一miRNA的序列不存在于任何動物的基因組中。也就是說，動物（包括人）永遠不可能自己轉(zhuǎn)錄產(chǎn)生這個miRNA。它本應(yīng)該只存在于植物中。然而，在一次無意中的實驗里，我們驚奇地發(fā)現(xiàn)小鼠血清中竟然存在這個miRNA。于是做了一系列的實驗，最后發(fā)現(xiàn)：食物一般的核酸和蛋白質(zhì)確實不能進入血液，但是miRNA，這一類特殊的調(diào)控分子，利用它極小的分子量和超常的穩(wěn)定性，能順利進入血液，并長期滯留，發(fā)揮其調(diào)控作用。而且，能夠通過母嬰傳播、能夠通過肉食進行間接傳遞。當(dāng)然，miR-A大量存在于大米中，我們吃了幾千年大米都沒事，說明這個因子是無害的。但是其他有很多miRNA是有著極其重大的調(diào)控作用的。比如miR-21，它是著名的原癌miRNA，幾乎所有的癌癥都有它參與。還有一些miRNA調(diào)控著胚胎和嬰兒的發(fā)育，包括骨骼肌肉大腦心臟等幾乎所有的臟器都受到miRNA的調(diào)控。如果它們從食物進入人體導(dǎo)致異常，那么就會產(chǎn)生畸形、人口素質(zhì)（大腦智力等）異常（倒不一定是下降......）等現(xiàn)象。這對轉(zhuǎn)基因食品是一個巨大的打擊。這一研究表明，轉(zhuǎn)基因食品的風(fēng)險還是存在的，依然有著很大的不可預(yù)見性。但是miRNA對一些生物因子的調(diào)控是很普遍的，比如前面提到的miR-21在癌癥中的作用，同為原癌miRNA的還有miR-31，miR-203等。miR-143是抑癌的，miR-221/222控制著細胞周期，miR-155與免疫和類風(fēng)濕性關(guān)節(jié)炎有關(guān)，等等。對于幼兒在母體中的胚胎發(fā)育，microRNA起著更重大的作用。miR-125a,miR-295,miR-219和miR-181b等等都與胚胎發(fā)育有關(guān)。miR-219過表達可以誘導(dǎo)胚胎細胞凋亡，基因沉默和過表達技術(shù)觀察到斑馬魚受精卵在顯微注射miR-219和反義miR-219后均導(dǎo)致其胚胎發(fā)育缺陷。miR-124a、miR-125b和miR-128的抑制會影響腦和脊髓的發(fā)育導(dǎo)致無腦兒。miR-124a/125b在感覺和運動神經(jīng)元發(fā)育過程中發(fā)揮作用。從現(xiàn)有文獻看，微小核糖核酸并非通過消化吸收而來。微小核糖核酸是由細胞自身表達，并作用于自身的調(diào)節(jié)物質(zhì) [1]。在異常細胞，如癌癥細胞中，存在微小核糖核酸異常表達。其因果關(guān)系為，細胞癌變導(dǎo)致了微小核糖核酸異常表達，而非微小核糖核酸異常表達導(dǎo)致癌癥。微小核糖核酸并不改變基因結(jié)構(gòu)，而是對基因的表達產(chǎn)生影響，故微小核糖核酸并不致癌。前文所說的，微小核糖核酸能被完整吸收并導(dǎo)致癌癥等疾病，并無可靠文獻證明?？缥锓N謀殺播報編輯通過給小鼠喂食生大米，科學(xué)家發(fā)現(xiàn)它們的血液和肝臟中，MIR168a的濃度確實因為飲食中MIR168a的增加而增加了。增加后會產(chǎn)生什么其他的影響呢？要預(yù)測植物微小RNA的增加能造成什么樣的生理結(jié)果，得先明白微小RNA是如何工作的。在細胞里，DNA像寫滿遺傳信息的藍圖，在適當(dāng)?shù)臅r候被“復(fù)印”成信使RNA（mRNA），再去指導(dǎo)蛋白質(zhì)的合成。而微小RNA就像殺手，非常有目標(biāo)地找到自己要謀殺的信使RNA，讓它們沒法繼續(xù)變出蛋白質(zhì)。當(dāng)然，微小RNA找目標(biāo)不看照片，而是看信使RNA和它的匹配度，要是信使RNA上某些片段它們恰好能結(jié)合上去，這些信使RNA就被視為該死的目標(biāo)。那么來自植物的MIR156a和MIR168a在動物體內(nèi)的謀殺目標(biāo)是誰呢？MIR168a經(jīng)過序列比對，科學(xué)家們推測，它在動物體內(nèi)確實有一個信使RNA目標(biāo)，這個信使RNA指導(dǎo)合成“綁架”低密度脂蛋白的蛋白，這個綁架者主要分布在肝臟。也就是說，MIR156a和MIR168a這個微小RNA專門對付綁架者，MIR168a若是升高了，肝臟里綁架者就少了，低密度脂蛋白不受綁架，在血液里的濃度就會慢慢積累變高。果然，他們發(fā)現(xiàn)，吃了大米以后，小鼠體內(nèi)MIR168a很快升高，3天后，血液中低密度脂蛋白膽固醇也變多了。這一切都驗證了張辰宇的猜想，同時讓科學(xué)界難以置信：來自植物的微小RNA竟然是一個超級殺手，可以跨物種執(zhí)行謀殺任務(wù)！機制研究播報編輯根據(jù)以前的研究，張辰宇知道血液中的小囊泡可以把微小RNA裝載起來，運送到身體其他部分，于是他猜測，小腸絨毛也可能把游離在附近的來自植物的微小RNA吞進來，包裹進小囊泡，再吐到血管里。隨后，囊泡順流而下，若是行至肝臟，這些囊泡可能被肝細胞吸收，微小RNA被釋放，于是結(jié)合它的目標(biāo)信使RNA，讓低密度脂蛋白的綁架者減少，造成血液里的壞膽固醇升高。這個過程聽起來像破案故事一樣激動人心！然而要想證明卻非易事——想想，怎么才可能親眼看到這個過程呢？科學(xué)家們也還沒能在完整的生物體里證實這個猜想，只能說向這個方向做出了努力。張辰宇團隊使用人體細胞模擬了上述場景。他們首先把大量合成的MIR168a微小RNA“喂”給體外培養(yǎng)的（也就是在平皿里培養(yǎng)的）人上皮細胞（小腸絨毛就是一種上皮細胞）。接著收集這些上皮細胞分泌的小囊泡。再轉(zhuǎn)移給在另一個平皿里培養(yǎng)的肝臟細胞。然后他們發(fā)現(xiàn)， MIR168a所要謀殺的綁架者在肝臟細胞里的量果然減少了。這樣的細胞實驗確實證明了張辰宇的猜想的機制是可行的，然而它畢竟是在相互分隔的兩種培養(yǎng)細胞之間做的，而不是在生物體的層面，所以這套機制只是被初步驗證，遠非確鑿。想要確鑿地說清植物微小RNA對人體的作用機制，還有待更精彩的實驗。由于張辰宇的研究顛覆常識，而且在幾十種存活于人體的植物微小RNA中，只發(fā)現(xiàn)MIR168a這一種會對動物產(chǎn)生作用，因此有人認為他的結(jié)果或許是巧合。來自捷克科學(xué)院分子遺傳學(xué)研究所（Institute of Molecular Genetics in the Czech Republic ）的Petr Svoboda認為，在張辰宇的實驗中，植物的微小RNA在人體內(nèi)檢測到的量很少，這個濃度的微小RNA是否真的能對人體產(chǎn)生影響值得懷疑。新手上路成長任務(wù)編輯入門編輯規(guī)則本人編輯我有疑問內(nèi)容質(zhì)疑在線客服官方貼吧意見反饋投訴建議舉報不良信息未通過詞條申訴投訴侵權(quán)信息封禁查詢與解封?2024?Baidu?使用百度前必讀?|?百科協(xié)議?|?隱私政策?|?百度百科合作平臺?|?京ICP證030173號?京公網(wǎng)安備110000020000

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An overview of microRNAs: Biology, functions, therapeutics, and analysis methods - PubMed

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miRNAs - Latest research and news | Nature

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Definition

micro RNAs (miRNAs) are a type of non-coding RNA (ncRNA), ~21?24 nucleotides in length, that function in the post-transcriptional regulation of gene expression. Typically miRNAs interact with specific mRNAs through complementary base-pairing to influence the translation or stability of the target mRNA molecule.

Latest Research and Reviews

MicroRNA-221-3p inhibits the inflammatory response of keratinocytes by regulating the DYRK1A/STAT3 signaling pathway to promote wound healing in diabetes

The microRNA miR-221-3p inhibits the inflammatory response and promotes skin wound healing in diabetes by targeting DYRK1A expression, thereby regulating the DYRK1A/STAT3 signaling pathway.

Keyan HuLei LiuQiu Zhang

ResearchOpen Access09 Mar 2024

Communications Biology

Volume: 7, P: 300

LncRNA-SNHG5 mediates activation of hepatic stellate cells by regulating NF2 and Hippo pathway

LncRNA SNHG5 can regulate the Hippo pathway and EMT process by interacting with NF2 to mediate the activation of hepatic stellate cells.

Rongrong ZhangYating ZhanJianjian Zheng

ResearchOpen Access04 Mar 2024

Communications Biology

Volume: 7, P: 266

An essential role for the RNA helicase DDX6 in NMDA receptor-dependent gene silencing and dendritic spine shrinkage

Fathima M. PerooliKevin A. WilkinsonJonathan G. Hanley

ResearchOpen Access06 Feb 2024

Scientific Reports

Volume: 14, P: 3066

Tissue-specific profiling of age-dependent miRNAomic changes in Caenorhabditis elegans

Wang et al. profile age-dependent miRNAomic changes in worm tissues and extracellular vesicles (EVs). They show that ageing controls miRNAs in a tissue-specific manner and their findings further suggest a complex EV-mediated miRNA trafficking network across tissues.

Xueqing WangQuanlong JiangYidong Shen

ResearchOpen Access01 Feb 2024

Nature Communications

Volume: 15, P: 955

Circular RNA cVIM promotes hepatic stellate cell activation in liver fibrosis via miR-122-5p/miR-9-5p-mediated TGF-β signaling cascade

The circRNA cVIM may act as a sponge for miR-122-5p and miR-9-5p to enhance expression of TGFBR1 and TGFBR2 and promote activation of the TGF-β/Smad pathway, thereby accelerating the progression of liver fibrosis.

Zhenxu ZhouRongrong ZhangJianjian Zheng

ResearchOpen Access19 Jan 2024

Communications Biology

Volume: 7, P: 113

Screening and validation of optimal miRNA reference genes in different developing stages and tissues of Lilium henryi Baker

Ge JinXiuhai ZhangMingfang Zhang

ResearchOpen Access17 Jan 2024

Scientific Reports

Volume: 14, P: 1545

All Research & Reviews

News and Comment

A catalytic function for mammalian Argonautes

Joana Vidigal reminds us of the first paper to report an endogenous role of the nucleolytic activity of the mammalian RNAi protein argonaute-2.

Joana A. Vidigal

Research Highlights14 Feb 2024

Nature Reviews Molecular Cell Biology

P: 1

o8G modifications rewire tumoral microRNAs

RNA modifications have emerged as key gene regulators. A new study shows that increased levels of reactive oxygen species in cancer induce widespread, sequence-specific modifications of guanines in the seed regions of microRNAs, altering the targets of those miRNAs and influencing tumorigenesis.

Marta MontesMaite Huarte

News & Views07 Sept 2023

Nature Cell Biology

Volume: 25, P: 1243-1244

microRNAs as systemic regulators of ageing

Wagner et al. report an organism-wide map of non-coding RNA expression in ageing and rejuvenated mice, identifying a set of broadly deregulated microRNAs that may act as systemic regulators of ageing.

Linda Koch

Research Highlights10 May 2023

Nature Reviews Genetics

Volume: 24, P: 415

First demonstration of miRNA-dependent mRNA decay

Marina Chekulaeva describes the experiments that showed that microRNAs cause degradation of their target mRNAs.

Marina Chekulaeva

Research Highlights14 Nov 2022

Nature Reviews Molecular Cell Biology

Volume: 24, P: 164

Target-directed microRNA degradation in Drosophila

A report in Molecular Cell identifies six new triggers of target-directed miRNA degradation, which are essential for normal Drosophila melanogaster embryogenesis.

Dorothy Clyde

Research Highlights07 Oct 2022

Nature Reviews Genetics

Volume: 23, P: 713

microRNAs in aged sperm confer psychiatric symptoms to offspring through causing the dysfunction of estradiol signaling in early embryos

Gaoli LiangXiaoju ZhuXi Chen

CorrespondenceOpen Access05 Jul 2022

Cell Discovery

Volume: 8, P: 63

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