Coordinated regulation of RNA polymerase II pausing and elongation progression by PAF1

被引：27

作者：

Wang, Zhenning ^{[1
,2
]}

Song, Aixia ^{[1
,2
]}

Xu, Hao ^{[1
,2
]}

Hu, Shibin ^{[1
,2
]}

Tao, Bolin ^{[1
,2
]}

Peng, Linna ^{[1
,2
]}

Wang, Jingwen ^{[1
,2
,3
]}

Li, Jiabei ^{[1
,2
]}

Yu, Jiali ^{[1
,2
]}

Wang, Li ^{[1
,2
]}

Li, Ze ^{[1
,2
]}

Chen, Xizi ^{[1
,2
]}

Wang, Mengyun ^{[1
,2
,3
]}

Chi, Yayun ^{[4
]}

Wu, Jiong ^{[4
]}

Xu, Yanhui ^{[1
,2
]}

Zheng, Hai ^{[1
,2
]}

Chen, Fei Xavier ^{[1
,2
,3
]}

机构：

[1] Fudan Univ, Shanghai Canc Ctr, Shanghai, Peoples R China

[2] Fudan Univ, Shanghai Key Lab Med Epigenet, Int Colab Med Epigenet & Metab, Minist Sci & Technol,Inst Biomed Sci, Shanghai, Peoples R China

[3] Shanghai Key Lab Radiat Oncol, Shanghai, Peoples R China

[4] Fudan Univ, Dept Breast Surg, Shanghai Canc Ctr, Shanghai, Peoples R China

来源：

SCIENCE ADVANCES | 2022年 / 8卷 / 13期

基金：

国家重点研发计划; 中国国家自然科学基金;

关键词：

TRANSCRIPTION ELONGATION; SACCHAROMYCES-CEREVISIAE; STRUCTURAL BASIS; READ ALIGNMENT; POL II; COMPLEX; ROLES; METHYLATION; RECRUITMENT; DISTINCT;

D O I：

10.1126/sciadv.abm5504

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Pleiotropic transcription regulator RNA polymerase II (Pol II)-associated factor 1 (PAF1) governs multiple transcriptional steps and the deposition of several epigenetic marks. However, it remains unclear how ultimate transcriptional outcome is determined by PAF1 and whether it relates to PAF1-controlled epigenetic marks. We use rapid degradation systems and reveal direct PAF1 functions in governing pausing partially by recruiting Integrator-PP2A (INTAC), in addition to ensuring elongation. Following acute PAF1 degradation, most destabilized polymerase undergoes effective release, which presumably relies on skewed balance between INTAC and P-TEFb, resulting in hyperphosphorylated substrates including SPT5. Impaired Pol II progression during elongation, along with altered pause release frequency, determines the final transcriptional outputs. Moreover, PAF1 degradation causes a cumulative decline in histone modifications. These epigenetic alterations in chromatin likely further influence the production of transcripts from PAF1 target genes.

引用

页数：15

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