IntS6 and the Integrator phosphatase module tune the efficiency of select premature transcription termination events

被引：6

作者：

Fujiwara, Rina ^{[1
]}

Zhai, Si-Nan ^{[2
,3
,4
]}

Liang, Dongming ^{[5
]}

Shah, Aayushi P. ^{[1
]}

Tracey, Matthew ^{[5
]}

Ma, Xu-Kai ^{[3
,4
]}

Mendoza-Figueroa, Maria Sarai ^{[5
]}

Fields, Christopher J. ^{[1
]}

Meline, Michele C. ^{[5
]}

Tatomer, Deirdre C. ^{[5
]}

Yang, Li ^{[3
,4
]}

Wilusz, Jeremy E. ^{[1
]}

机构：

[1] Baylor Coll Med, Therapeut Innovat Ctr, Verna & Marrs McLean Dept Biochem & Mol Pharmacol, Houston, TX 77030 USA

[2] Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Nutr & Hlth, Shanghai 200031, Peoples R China

[3] Fudan Univ, Childrens Hosp, Ctr Mol Med, Shanghai 200032, Peoples R China

[4] Fudan Univ, Minist Sci & Technol, Shanghai Key Lab Med Epigenet, Inst Biomed Sci,Int Lab Med Epigenet & Metab, Shanghai 200032, Peoples R China

[5] Univ Penn, Perelman Sch Med, Dept Biochem & Biophys, Philadelphia, PA 19104 USA

来源：

MOLECULAR CELL | 2023年 / 83卷 / 24期

基金：

美国国家卫生研究院; 中国国家自然科学基金;

关键词：

COMPLEX; EXPRESSION; 2A; SNRNA; ALIGNMENT; SUBUNIT; ACTIVATION; MECHANISM; RECRUITS; PACKAGE;

D O I：

10.1016/j.molcel.2023.10.035

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The metazoan-specific Integrator complex catalyzes 30 end processing of small nuclear RNAs (snRNAs) and premature termination that attenuates the transcription of many protein-coding genes. Integrator has RNA endonuclease and protein phosphatase activities, but it remains unclear if both are required for complex function. Here, we show IntS6 (Integrator subunit 6) over-expression blocks Integrator function at a subset of Drosophila protein-coding genes, although having no effect on snRNAs or attenuation of other loci. Over-expressed IntS6 titrates protein phosphatase 2A (PP2A) subunits, thereby only affecting gene loci where phosphatase activity is necessary for Integrator function. IntS6 functions analogous to a PP2A regulatory B subunit as over-expression of canonical B subunits, which do not bind Integrator, is also sufficient to inhibit Integrator activity. These results show that the phosphatase module is critical at only a subset of Integrator-regulated genes and point to PP2A recruitment as a tunable step that modulates transcription termination efficiency.

引用

页码：4445 / 4460.e7

页数：24