DSIF and NELF interact with Integrator to specify the correct post-transcriptional fate of snRNA genes
DSIF and NELF interact with Integrator to specify the correct post-transcriptional fate of snRNA genes
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DOI：
10.1038/ncomms5263
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发表时间：
2014-06-01
影响因子：
16.6
通讯作者：
Yamaguchi, Yuki
中科院分区：
文献类型：
--
作者：
Yamamoto, Junichi;Hagiwara, Yuri;Yamaguchi, Yuki
延伸因子DSIF和NELF负责启动子近端RNA聚合酶II（Pol II）暂停。NELF还参与复制依赖性组蛋白基因的3'加工，其产生非聚腺苷酸化的mRNA。在这里，我们表明DSIF和NELF通过与Integrator（负责前snRNA 3'加工的大型多亚基复合物）的结合促进小核RNA（snRNA）的合成。在HeLa细胞中，Pol II、Integrator、DSIF和NELF积累在U1 snRNA基因的3'末端。NELF的敲低导致U1、U2、U4和U5 snRNA的错误加工，而DSIF是这些基因正确转录所必需的。敲除NELF还破坏转录终止并诱导由切割刺激因子增强募集引起的多聚腺苷酸化U1转录本的产生。我们的研究结果表明，NELF起着关键作用，在决定转录后的命运Pol II转录基因。
The elongation factors DSIF and NELF are responsible for promoter-proximal RNA polymerase II (Pol II) pausing. NELF is also involved in 3' processing of replication-dependent histone genes, which produce non-polyadenylated mRNAs. Here we show that DSIF and NELF contribute to the synthesis of small nuclear RNAs (snRNAs) through their association with Integrator, the large multisubunit complex responsible for 3' processing of pre-snRNAs. In HeLa cells, Pol II, Integrator, DSIF and NELF accumulate at the 3' end of the U1 snRNA gene. Knockdown of NELF results in misprocessing of U1, U2, U4 and U5 snRNAs, while DSIF is required for proper transcription of these genes. Knocking down NELF also disrupts transcription termination and induces the production of polyadenylated U1 transcripts caused by an enhanced recruitment of cleavage stimulation factor. Our results indicate that NELF plays a key role in determining the post-transcriptional fate of Pol II-transcribed genes.