On the importance of being co-transcriptional
On the importance of being co-transcriptional
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DOI：
10.1242/jcs.00073
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发表时间：
2002-10-15
影响因子：
4
通讯作者：
Neugebauer, KM
中科院分区：
文献类型：
--
作者：
Neugebauer, KM
近年来的深入研究表明，许多前mRNA加工事件是共转录的，或者至少在RNA聚合酶II（Pol II）的RNA合成期间开始。但是前mRNA的加工是以共转录的方式发生的，这重要吗？尽管Pol II通过结合并募集所有三种加帽活性至转录单位来指导mRNA的5'加帽，但共转录剪接不是强制性的。在某些情况下，如选择性剪接，剪接可能发生在转录后，因为剪接不利内含子的动力学较慢。尽管最近的模型中，剪接因子直接绑定到C-末端结构域（CTD）的Pol II，很少有证据支持这一观点。相反，snRNP和转录延伸因子之间的相互作用为转录和剪接之间的物理联系提供了最强有力的分子证据。转录终止依赖于多聚腺苷酸化信号，但是，像剪接一样，多聚腺苷酸化本身可能在共转录时开始并在转录后继续。新生RNA在决定哪些转录本是多聚腺苷酸化的以及使用哪一个替代末端外显子方面起着重要作用。最近增加的共转录RNA加工是一个可能的RNA监视步骤之前释放的mRNP从转录单位，这似乎是协调核转运与mRNA加工，并可能是由核外泌体的成分介导的。
Intense research in recent years has shown that many pre-mRNA processing events are co-transcriptional or at least begin during RNA synthesis by RNA polymerase II (Pol II). But is it important that pre-mRNA processing occurs co-transcriptionally? Whereas Pol II directs 5' capping of mRNA by binding to and recruiting all three capping activities to transcription units, co-transcriptional splicing is not obligatory. In some cases, such as alternative splicing, splicing may occur post-transcriptionally owing to the slower kinetics of splicing unfavorable introns. Despite recent models in which splicing factors are bound directly to the C-terminal domain (CTD) of Pol II, little evidence supports that view. Instead, interactions between snRNPs and transcription elongation factors provide the strongest molecular evidence for a physical link between transcription and splicing. Transcription termination depends on polyadenylation signals, but, like splicing, polyadenylation per se probably begins co-transcriptionally and continues post-transcriptionally. Nascent RNA plays an important role in determining which transcripts are polyadenylated and which alternative terminal exon is used. A recent addition to co-transcriptional RNA processing is a possible RNA surveillance step prior to release of the mRNP from the transcription unit, which appears to coordinate nuclear transport with mRNA processing and may be mediated by components of the nuclear exosome.