Widespread intron retention in mammals functionally tunes transcriptomes.
Widespread intron retention in mammals functionally tunes transcriptomes.
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DOI：
10.1101/gr.177790.114
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发表时间：
2014-11
期刊：
影响因子：
7
通讯作者：
Blencowe BJ
中科院分区：
文献类型：
--
作者：
Braunschweig U;Barbosa-Morais NL;Pan Q;Nachman EN;Alipanahi B;Gonatopoulos-Pournatzis T;Frey B;Irimia M;Blencowe BJ
前体RNA的选择性剪接（AS）极大地扩展了真核生物基因组的调控和功能能力。在不同类型的AS中，内含子保留（IR）是最不了解的。在植物和单细胞真核生物中，IR是AS最常见的形式，而在动物中，它被认为是最不常见的形式。使用高覆盖率的poly（A）+ RNA-seq数据，我们观察到IR在哺乳动物中惊人地频繁，影响多达四分之三的多外显子基因的转录本。包含“IR代码”的一组高度相关的顺式特征可靠地将保留的内含子与组成性剪接的内含子区分开。我们表明，IR广泛地作用于降低转录物的水平，这些转录物对于检测到它们的细胞或组织类型的生理学是较少或不需要的。IR的这种“转录组调节”功能通过无义介导的mRNA衰变和IR转录物的核螯合和周转两者起作用。我们进一步表明，IR与涉及RNA聚合酶II（Pol II）的局部停滞和剪接体组分的可用性降低的串扰机制有关。总的来说，这些结果涉及一个全球检查点型机制，即减少招募剪接组件耦合到Pol II暂停的基础广泛IR介导的抑制不适当表达的转录。
Alternative splicing (AS) of precursor RNAs is responsible for greatly expanding the regulatory and functional capacity of eukaryotic genomes. Of the different classes of AS, intron retention (IR) is the least well understood. In plants and unicellular eukaryotes, IR is the most common form of AS, whereas in animals, it is thought to represent the least prevalent form. Using high-coverage poly(A)+ RNA-seq data, we observe that IR is surprisingly frequent in mammals, affecting transcripts from as many as three-quarters of multiexonic genes. A highly correlated set of cis features comprising an “IR code” reliably discriminates retained from constitutively spliced introns. We show that IR acts widely to reduce the levels of transcripts that are less or not required for the physiology of the cell or tissue type in which they are detected. This “transcriptome tuning” function of IR acts through both nonsense-mediated mRNA decay and nuclear sequestration and turnover of IR transcripts. We further show that IR is linked to a cross-talk mechanism involving localized stalling of RNA polymerase II (Pol II) and reduced availability of spliceosomal components. Collectively, the results implicate a global checkpoint-type mechanism whereby reduced recruitment of splicing components coupled to Pol II pausing underlies widespread IR-mediated suppression of inappropriately expressed transcripts.
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影响因子：
16
作者：
Chathoth, Keerthi T.;Barrass, J. David;Webb, Shaun;Beggs, Jean D.
通讯作者：
Beggs, Jean D.
影响因子：
14.9
作者：
Dreszer TR;Karolchik D;Zweig AS;Hinrichs AS;Raney BJ;Kuhn RM;Meyer LR;Wong M;Sloan CA;Rosenbloom KR;Roe G;Rhead B;Pohl A;Malladi VS;Li CH;Learned K;Kirkup V;Hsu F;Harte RA;Guruvadoo L;Goldman M;Giardine BM;Fujita PA;Diekhans M;Cline MS;Clawson H;Barber GP;Haussler D;James Kent W
通讯作者：
James Kent W
影响因子：
14.9
作者：
Flicek P;Ahmed I;Amode MR;Barrell D;Beal K;Brent S;Carvalho-Silva D;Clapham P;Coates G;Fairley S;Fitzgerald S;Gil L;García-Girón C;Gordon L;Hourlier T;Hunt S;Juettemann T;Kähäri AK;Keenan S;Komorowska M;Kulesha E;Longden I;Maurel T;McLaren WM;Muffato M;Nag R;Overduin B;Pignatelli M;Pritchard B;Pritchard E;Riat HS;Ritchie GR;Ruffier M;Schuster M;Sheppard D;Sobral D;Taylor K;Thormann A;Trevanion S;White S;Wilder SP;Aken BL;Birney E;Cunningham F;Dunham I;Harrow J;Herrero J;Hubbard TJ;Johnson N;Kinsella R;Parker A;Spudich G;Yates A;Zadissa A;Searle SM
通讯作者：
Searle SM
影响因子：
4.5
作者：
Galante, PAF;Sakabe, NJ;De Souza, SJ
通讯作者：
De Souza, SJ
影响因子：
3.6
作者：
David, Charles J.;Manley, James L.
通讯作者：
Manley, James L.