Decoding the 3′End: Integrative Transcriptomics of Aberrant and Alternative Transcription Termination
HSV-1 infection leads to genome-wide disruption of transcription termination but also increased use of internal poly(A) sites within genes similar to what is observed upon inhibition of splicing. To disentangle disrupted, premature and alternative transcription termination requires precise determination of poly(A) site locations before and during infection or splicing inhibition combined with transcriptomics of nascent transcription. In this talk, I will present methods we developed for integrative analysis of these data as well as results from our studies on HSV-1 transcription termination and CDK11 inhibition, which inhibits splicing genome-wide. In this way, we showed that premature and disrupted transcription termination in HSV-1 infection depends on only partially overlapping pathways and distinct functions of viral proteins.