Children’s Nutrition Research Center Staff Publications

Language

English

Publication Date

12-21-2023

Journal

Molecular Cell

DOI

10.1016/j.molcel.2023.10.035

PMID

37995689

PMCID

PMC10841813

PubMedCentral® Posted Date

11-21-2024

PubMedCentral® Full Text Version

Author MSS

Abstract

The metazoan-specific Integrator complex catalyzes 3' 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.

Keywords

Animals, RNA, RNA Polymerase II, RNA, Small Nuclear, Transcription Factors, Drosophila Proteins, Drosophila melanogaster, Transcription Termination, Genetic

Published Open-Access

yes

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