IntS6 and the Integrator phosphatase module tune the efficiency of select premature transcription termination events. Fujiwara et al.

Published: 10 November 2023| Version 1 | DOI: 10.17632/r46b2sgkkb.1
Contributors:
Jeremy Wilusz, Rina Fujiwara, Si-Nan Zhai, Dongming Liang, Matthew Tracey, Xu-Kai Ma, Aayushi Shah, Christopher Fields, Maria Sarai Mendoza-Figueroa, Michele Meline, Deirdre Tatomer, Li Yang

Description

The metazoan-specific Integrator complex catalyzes 3' end processing of small nuclear RNAs (snRNAs) and premature termination that attenuates 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, while 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, are 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.

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Institutions

University of Pennsylvania, Baylor College of Medicine, Fudan University

Categories

Transcription, RNA, Phosphatase, Termination of Transcription

Funding

National Institute of General Medical Sciences

R35-GM119735

Cancer Prevention and Research Institute of Texas

RR210031

National Natural Science Foundation of China

31925011

Licence