Alternative RNA structures formed during transcription depend on elongation rate and modify RNA processing.
Alternative RNA structures formed during transcription depend on elongation rate and modify RNA processing.
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在转录过程中形成的替代RNA结构取决于延伸速率和修饰RNA加工。
DOI：
10.1016/j.molcel.2021.01.040
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发表时间：
2021-04-15
期刊：
影响因子：
16
通讯作者：
Bentley DL
中科院分区：
文献类型：
--
作者：
Saldi T;Riemondy K;Erickson B;Bentley DL
大多数RNA加工都是以共转录方式进行的。我们通过化学和酶探针询问了新生PolII转录本，并确定了“新生RNA结构体”与剪接、A-I编辑和转录速度的关系。内含子内的RNA折叠和剪接点的陡峭结构转变与有效的共转录剪接有关。一个缓慢的polII突变体引起广泛的重塑，随着A-I编辑的增加而变成更多的折叠构象。在3‘剪接点变得更有结构的内含子可以更有效地协同转录切除。缓慢的PolII改变了内含子Alu元件的折叠，其中隐藏的剪接和内含子保留被刺激，这一结果被紫外线模仿，从而减慢转录。慢转录也以不同的方式重塑了RNA在可选外显子周围的折叠，从而预测是跳过还是包含更受青睐，即使它发生在转录后。因此，共转录RNA折叠调节转录后的选择性剪接。综上所述，新生转录产物的可塑性对RNA的加工有广泛的影响。生长中的前mRNAs的折叠如何影响它们的共转录过程？通过对新生RNA、PolII转录本的探测，Saldi等人确定了与有效的共转录剪接和A-I编辑相关的结构特征。慢转录以预测其对选择性剪接的影响的方式广泛地重塑新生RNA结构。
Most RNA processing occurs co-transcriptionally. We interrogated nascent pol II transcripts by chemical and enzymatic probing, and determined how the “nascent RNA structureome” relates to splicing, A-I editing and transcription speed. RNA folding within introns and steep structural transitions at splice sites are associated with efficient co-transcriptional splicing. A slow pol II mutant elicits extensive remodeling into more folded conformations with increased A-I editing. Introns that become more structured at their 3’ splice sites get co-transcriptionally excised more efficiently. Slow pol II altered folding of intronic Alu elements where cryptic splicing and intron retention are stimulated, an outcome mimicked by UV which decelerates transcription. Slow transcription also remodeled RNA folding around alternative exons in distinct ways that predict whether skipping or inclusion is favored, even though it occurs post-transcriptionally. Hence co-transcriptional RNA folding modulates post-transcriptional alternative splicing. In summary the plasticity of nascent transcripts has widespread effects on RNA processing. How does the folding of growing pre-mRNAs affect their co-transcriptional processing? By probing of nascent RNA pol II transcripts Saldi et al identify structural features associated with efficient co-transcriptional splicing and A-I editing. Slow transcription extensively remodels nascent RNA structures in ways that predict its effects on alternative splicing.
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影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
DOI：
10.1093/bioinformatics/btp250
发表时间：
2009-08-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Darty K;Denise A;Ponty Y
通讯作者：
Ponty Y
影响因子：
16
作者：
Dujardin, Gwendal;Lafaille, Celina;Kornblihtt, Alberto R.
通讯作者：
Kornblihtt, Alberto R.
影响因子：
16.8
作者：
Ameur, Adam;Zaghlool, Ammar;Feuk, Lars
通讯作者：
Feuk, Lars
影响因子：
7
作者：
Aslanzadeh V;Huang Y;Sanguinetti G;Beggs JD
通讯作者：
Beggs JD