Regulation of Eukaryotic RNAPs Activities by Phosphorylation

Evolutionarily conserved kinases and phosphatases regulate RNA polymerase II (RNAPII) transcript synthesis by modifying the phosphorylation status of the carboxyl-terminal domain (CTD) of Rpb1, the largest subunit of RNAPII. Proper levels of Rpb1-CTD phosphorylation are required for RNA co-transcriptional processing and to coordinate transcription with other nuclear processes, such as chromatin remodeling and histone modification. Whether other RNAPII subunits are phosphorylated and influences their role in gene expression is still an unanswered question. Much less is known about RNAPI and RNAPIII phosphorylation, whose subunits do not contain functional CTDs. However, diverse studies have reported that several RNAPI and RNAPIII subunits are susceptible to phosphorylation. Some of these phosphorylation sites are distributed within subunits common to all three RNAPs whereas others are only shared between RNAPI and RNAPIII. This suggests that the activities of all RNAPs might be finely modulated by phosphorylation events and raises the idea of a tight coordination between the three RNAPs. Supporting this view, the transcription by all RNAPs is regulated by signaling pathways that sense different environmental cues to adapt a global RNA transcriptional response. This review focuses on how the phosphorylation of RNAPs might regulate their function and we comment on the regulation by phosphorylation of some key transcription factors in the case of RNAPI and RNAPIII. Finally, we discuss the existence of possible common mechanisms that could coordinate their activities.Funding was provided by the Spanish Ministry of Economy and Competitiveness (MINECO) and ERDF with Grants conceded to OC (BFU2017-84694-P), AC-B (PGC2018-097963-B-100), FN (BFU2016-77728-C3-2-P), and by Spanish Ministry of Science and Innovation (MICINN) and ERDF to OC and FN (RED2018-102467-T); and by the Junta de Andalucía-Universidad de Jaén (FEDER-UJA 1260360), and the Junta de Andalucía (BIO258) to FN, AG-J, and AC were supported by pre-doctoral contracts from “Junta de Castilla y León”. The IBFG is supported in part by an institutional grant from the “Junta y Castilla y León” (Programa “Escalera de Excelencia” de la Junta de Castilla y León, CLU-2017-03), cofunded by ERDF OP de Castilla y León 14-20