New functions for Sub1 in RNAPII transcriptin regulation

GARAVÍS, MIGUEL; COLLIN, ALEJANDRO; ALLEPUZ-FUSTER, PAULA; ALONSO-AGUADO, SERGIO; GARCÍA-AGUDO, MARÍA; POLO, NOELIA; CALVO, OLGA

Sant Feliu de Guixols

Congreso; Gene Transcrition in Yeast: From Chromatin to RNA and back; 2016

EMBO

Sub1 is an evolutionary conserved factor that was originally described as a transcriptional stimulatory protein based on its capacity to bind TFIIB, and its homology to human positive coactivator PC4. Recently, orthologues of PC4/Sub1 have been also identified in procaryotes. Sub1 has been implicated in many processes during mRNA biogenesis: (I) It is a functional component of the preinitiation complex. (II) ySub1/hPC4 links transcription initiation to termination and 3´-end processing, via the interaction with a polyadenilation factor. (III) Sub1 associates with Spt5 to influence transcription elongation rate and it globally modulates RNAP II-CTD phosphorylation. (IV) Latelly, it has been proposed a role for Sub1 during osmotic and oxidative stress. Apart from its multiple roles in mRNA transcription and processing, both Sub1 and PC4 are also involved in transcription by RNAPIII. Moreover, PC4 and Sub1 have been implicated in other DNA-dependent processes beyond transcription, such as DNA repair and replication. Although many functions have been shown for Sub1, the exact molecular mechanisms through which it plays its different roles in mRNA biogenesis are mostly unknown. We have done novel discoveries about Sub1 that add new insight into its function during RNAPII transcription. For instance, Sub1 requires a 12-subunit RNAPII to be effectively recruited to gene promoters. We also show that Sub1 levels are important for cell recovery from several stress conditions, and that they are regulated by the Srb10 kinase, a component of the Mediator CDK module.