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
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


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.



University of Pennsylvania, Baylor College of Medicine, Fudan University


Transcription, RNA, Phosphatase, Termination of Transcription


National Institute of General Medical Sciences


Cancer Prevention and Research Institute of Texas


National Natural Science Foundation of China