The 3′ Pol II pausing at replication-dependent histone genes is regulated by Mediator through Cajal bodies' association with histone locus bodies

Transcription termination is generally accompanied by the 3 '-end processing of transcripts. Here the authors demonstrate a role for Mediator in transcript end site proximal pausing of replication-dependent histone genes. Non-polyadenylated mRNAs of replication-dependent histones (RDHs) are synthesized by RNA polymerase II (Pol II) at histone locus bodies (HLBs). HLBs frequently associate with Cajal bodies (CBs), in which 3 '-end processing factors for RDH genes are enriched; however, this association's role in transcription termination of RDH genes remains unclear. Here, we show that Pol II pauses immediately upstream of transcript end sites of RDH genes and Mediator plays a role in this Pol II pausing through CBs' association with HLBs. Disruption of the Mediator docking site for Little elongation complex (LEC)-Cap binding complex (CBC)-Negative elongation factor (NELF), components of CBs, interferes with CBs' association with HLBs and 3 ' Pol II pausing, resulting in increased aberrant unprocessed RDH gene transcripts. Our findings suggest Mediator's involvement in CBs' association with HLBs to facilitate 3 ' Pol II pausing and subsequent 3 '-end processing of RDH genes by supplying 3 '-end processing factors.

Automated summary

This study demonstrates the importance of Mediator in the transcription termination of replication-dependent histone genes. Mediator plays a role in pausing RNA polymerase II at the transcript end sites of these genes by associating with Cajal bodies, thereby facilitating the subsequent 3'-end processing.