Termination of protein-coding gene transcription by RNA polymerase II (Pol II) depends on endonucleolytic cleavage at the poly(A) site and the activity of a 5->3 torpedo exoribonuclease. Other Pol II transcripts also undergo endonucleolytic cleavage suggesting common themes for its termination. Nevertheless, many RNA polymerases employ intrinsic/allosteric termination that directly defines transcript 3 ends. We have analysed termination of snRNA transcription in humans, which utilises the endoribonucleolytic integrator complex. Integrator is involved, but termination continues after its depletion. This implicates additional mechanisms and shows that endo- and 5->3 exonuclease activities are not necessarily a basis for all Pol II termination. Although the alternative process acts as a failsafe in the absence of integrator it contributes significantly to snRNA termination in the natural situation. Long-read sequencing reveals its products to have stochastic 3 ends that are terminated before integrator cleavage, ruling out 5->3 exonuclease contribution(s) and supporting an allosteric/intrinsic mechanism. Termination of some snRNA transcription occurs at T-runs further indicating common principles between this mechanism and those used by other RNA polymerases. SOURCE: Steven West (s.west@exeter.ac.uk) -  University of Exeter

Pluto Bioinformatics

GSE150238: An allosteric/intrinsic mechanism supports termination of snRNA transcription.