2022-01-182022-01-182021-12December 2https://hdl.handle.net/2152.3/11363The Integrator complex is a 14-subunit protein complex that interacts with RNA polymerase II (RNAPII) in metazoans during transcription of multiple forms of coding and non-coding RNA. Originally described as being responsible for the 3’ cleavage and termination of uridine-rich small nuclear RNA, further roles have been discovered in the cleavage of long non-coding RNA, enhancer RNA, telomerase RNA, and coding messenger RNAs. While many studies have identified a presence at the transcriptional start site of mRNA, Integrator’s function at these mRNA has yet to be identified. In this study, we used multiple biochemical and sequencing techniques to elucidate a role for Integrator at these mRNA start sites. We found that the endonuclease activity of Integrator subunit 11 (IntS11) was responsible for the attenuation of mRNA through promoter-proximal termination of a large set of paused mRNAs. We also identified a novel interaction between IntS11 and CG7044 that could inhibit IntS11’s endonuclease activity.application/pdfRNA biology, TranscriptionThesis2022-01-18