SPT6 functions in transcriptional pause/release via PAF1C recruitment.
SPT6 functions in transcriptional pause/release via PAF1C recruitment.
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DOI：
10.1016/j.molcel.2022.06.037
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发表时间：
2022-09-15
期刊：
影响因子：
16
通讯作者：
Shilatifard, Ali
中科院分区：
文献类型：
--
作者：
Aoi, Yuki;Shah, Avani P.;Ganesan, Sheetal;Soliman, Shimaa H. A.;Cho, Byoung-Kyu;Goo, Young Ah;Kelleher, Neil L.;Shilatifard, Ali
目前还不清楚各种因素在转录延长RNA聚合酶II（RNA Pol II）合作调节暂停/释放和生产性延长活细胞。使用急性蛋白质消耗的方法，我们报告说，SPT 6消耗的结果，暂停RNA Pol II释放到基因体通过受损的招聘PAF 1C。短基因表现出释放增加的成熟转录本，而长基因被释放，但不能产生成熟的转录本，由于减少的合成能力作为结果的SPT 6和PAF 1C的损失。出乎意料的是，SPT 6缺失导致NELF与基因体上的延伸RNA Pol II相关，而对转录延伸模式没有任何观察到的功能意义，从而反对NELF在保持RNA Pol II处于暂停状态中的作用。此外，SPT 6耗竭损害热休克诱导的暂停，指出SPT 6在调节RNA Pol II暂停/释放通过PAF 1C招聘的作用。Aoi等人发现转录延伸因子SPT 6通过在细胞中募集PAF 1复合物来调节启动子近端暂停的RNA聚合酶II的释放。SPT 6缺失导致RNA聚合酶II释放到基因体中，同时与负延伸因子NELF相关。
It is unclear how various factors functioning in transcriptional elongation by RNA polymerase II (RNA Pol II) cooperatively regulate pause/release and productive elongation in living cells. Using an acute protein depletion approach, we report that SPT6 depletion results in release of paused RNA Pol II into gene bodies through impaired recruitment of PAF1C. Short genes demonstrate a release with increased mature transcripts, whereas long genes are released but fail to yield mature transcripts, due to a reduced processivity as the result of both SPT6 and PAF1C loss. Unexpectedly, SPT6 depletion causes an association of NELF with the elongating RNA Pol II on gene bodies, without any observed functional significance on transcriptional elongation pattern, arguing against a role for NELF in keeping RNA Pol II in the paused state. Furthermore, SPT6 depletion impairs heat shock-induced pausing, pointing to a role of SPT6 in regulating RNA Pol II pause/release through PAF1C recruitment. Aoi et al find that transcription elongation factor SPT6 regulates the release of the promoter-proximal paused RNA polymerase II through recruitment of the PAF1 complex in cells. SPT6 loss results in the release of RNA polymerase II into gene bodies while associated with negative elongation factor NELF.
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影响因子：
64.5
作者：
Bai X;Kim J;Yang Z;Jurynec MJ;Akie TE;Lee J;LeBlanc J;Sessa A;Jiang H;DiBiase A;Zhou Y;Grunwald DJ;Lin S;Cantor AB;Orkin SH;Zon LI
通讯作者：
Zon LI
影响因子：
16
作者：
Doris, Stephen M.;Chuang, James;Winston, Fred
通讯作者：
Winston, Fred
影响因子：
16
作者：
Aoi Y;Takahashi YH;Shah AP;Iwanaszko M;Rendleman EJ;Khan NH;Cho BK;Goo YA;Ganesan S;Kelleher NL;Shilatifard A
通讯作者：
Shilatifard A
影响因子：
64.5
作者：
Chen FX;Woodfin AR;Gardini A;Rickels RA;Marshall SA;Smith ER;Shiekhattar R;Shilatifard A
通讯作者：
Shilatifard A
影响因子：
5.3
作者：
Fujinaga, K;Irwin, D;Peterlin, BM
通讯作者：
Peterlin, BM