Post-transcriptional 3´-UTR cleavage of mRNA transcripts generates thousands of stable uncapped autonomous RNA fragments.
Post-transcriptional 3´-UTR cleavage of mRNA transcripts generates thousands of stable uncapped autonomous RNA fragments.
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DOI：
10.1038/s41467-017-02099-7
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发表时间：
2017-12-11
影响因子：
16.6
通讯作者：
Berger M
中科院分区：
文献类型：
--
作者：
Malka Y;Steiman-Shimony A;Rosenthal E;Argaman L;Cohen-Daniel L;Arbib E;Margalit H;Kaplan T;Berger M
大多数哺乳动物基因含有一个或多个可选择的多聚腺苷酸化位点。多聚腺苷酸化位点的选择被认为是产生较长/较短转录异构体的潜在机制之一。在这里，我们证明了成熟的mRNA转录物可以在3′-UTR的近端内部位点进行额外的切割和多聚腺苷酸化，从而产生两个稳定的自主RNA片段：具有较短3′-UTR的编码序列（主体）和切割点下游的未加帽3′-UTR序列（尾部）。对人类转录组的分析揭示了数千个这样的切割位置，这表明一种广泛的转录后现象产生了数千个稳定的3′-UTR RNA尾，这些尾与它们的原始转录本一起存在。通过分析microRNA的影响，我们观察到与尾部片段相比，microRNA在体内的调节作用明显更强。我们的研究结果开辟了多种未来的研究前景，并呼吁对3′-UTR依赖的基因调控的新视角。大多数哺乳动物基因含有可选择的多聚腺苷酸化位点。在这里，作者提供的证据表明，mRNA可以在转录后被切割，产生具有较短3-′ UTR和稳定的自主无帽3 ′-UTR序列的mRNA。
The majority of mammalian genes contain one or more alternative polyadenylation sites. Choice of polyadenylation sites was suggested as one of the underlying mechanisms for generating longer/shorter transcript isoforms. Here, we demonstrate that mature mRNA transcripts can undergo additional cleavage and polyadenylation at a proximal internal site in the 3′-UTR, resulting in two stable, autonomous, RNA fragments: a coding sequence with a shorter 3′-UTR (body) and an uncapped 3′-UTR sequence downstream of the cleavage point (tail). Analyses of the human transcriptome has revealed thousands of such cleavage positions, suggesting a widespread post-transcriptional phenomenon producing thousands of stable 3′-UTR RNA tails that exist alongside their transcripts of origin. By analyzing the impact of microRNAs, we observed a significantly stronger effect for microRNA regulation at the body compared to the tail fragments. Our findings open a variety of future research prospects and call for a new perspective on 3′-UTR-dependent gene regulation. Most mammalian genes contain alternative polyadenylation sites. Here, the authors provide evidence that mRNA can be cleaved post-transcriptionally to generate mRNAs with shorter 3-´UTRs and stable autonomous uncapped 3´-UTR sequences.
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影响因子：
7
作者：
Neve J;Burger K;Li W;Hoque M;Patel R;Tian B;Gullerova M;Furger A
通讯作者：
Furger A
影响因子：
14.9
作者：
Mercer TR;Wilhelm D;Dinger ME;Soldà G;Korbie DJ;Glazov EA;Truong V;Schwenke M;Simons C;Matthaei KI;Saint R;Koopman P;Mattick JS
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影响因子：
4.5
作者：
Hoffman Y;Bublik DR;Ugalde AP;Elkon R;Biniashvili T;Agami R;Oren M;Pilpel Y
通讯作者：
Pilpel Y
影响因子：
16
作者：
Heinz S;Benner C;Spann N;Bertolino E;Lin YC;Laslo P;Cheng JX;Murre C;Singh H;Glass CK
通讯作者：
Glass CK
影响因子：
64.5
作者：
Mayr C;Bartel DP
通讯作者：
Bartel DP