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Mol Cell ; 83(24): 4445-4460.e7, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-37995689

RESUMO

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.


Assuntos
Proteínas de Drosophila , Terminação da Transcrição Genética , Animais , RNA , RNA Polimerase II/genética , RNA Polimerase II/metabolismo , RNA Nuclear Pequeno/genética , Fatores de Transcrição/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster
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