Fujiwara, R., Zhai, S.N., Liang, D., Shah, A.P., Tracey, M., Ma, X.K., Fields, C.J., Mendoza-Figueroa, M.S., Meline, M.C., Tatomer, D.C., Yang, L., Wilusz, J.E. (2023). IntS6 and the Integrator phosphatase module tune the efficiency of select premature transcription termination events.  Mol. Cell 83(24): 4445--4460.e7.

FBrf0258341

Research paper

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.

PMC10841813 (PMC) (EuropePMC)