The PAF1 complex promotes 3′ processing of pervasive transcripts

The PAF1 complex (PAF1C) functions in multiple transcriptional processes involving RNA polymerase II (RNA Pol II). Enhancer RNAs (eRNAs) and promoter upstream transcripts (PROMPTs) are pervasive transcripts transcribed by RNA Pol II and degraded rapidly by the nuclear exosome complex after 3' endonucleolytic cleavage by the Integrator complex (Integrator). Here we show that PAF1 C has a role in termination of eRNAs and PROMPTs that are cleaved 1-3 kb downstream of the transcription start site. Mechanistically, PAF1C facilitates recruitment of Integrator to sites of pervasive transcript cleavage, promoting timely cleavage and transcription termination. We also show that PAF1C recruits Integrator to coding genes, where PAF1C then dissociates from Integrator upon entry into processive elongation. Our results demonstrate a function of PAF1C in limiting the length and accumulation of pervasive transcripts that result from non-productive transcription.