Genome-Wide Regulations of the Preinitiation Complex Formation and Elongating RNA Polymerase II by an E3 Ubiquitin Ligase, San1
- 1 January 2022
- journal article
- research article
- Published by Taylor & Francis Ltd in Molecular and Cellular Biology
- Vol. 42 (1), e0036821
- https://doi.org/10.1128/mcb.00368-21
Abstract
San1 ubiquitin ligase is involved in nuclear protein quality control via its interaction with intrinsically disordered proteins for ubiquitylation and proteasomal degradation. Since several transcription/chromatin regulatory factors contain intrinsically disordered domains and can be inhibitory to transcription when in excess, San1 might be involved in transcription regulation. To address this, we analyzed the role of San1 in genome-wide association of TBP [that nucleates pre-initiation complex (PIC) formation for transcription initiation] and RNA polymerase II (Pol II). Our results reveal the roles of San1 in regulating TBP recruitment to the promoters and Pol II association with the coding sequences, and hence PIC formation and coordination of elongating Pol II, respectively. Consistently, transcription is altered in the absence of San1. Such transcriptional alteration is associated with impaired ubiquitylation and proteasomal degradation of Spt16 and gene association of Paf1, but not the incorporation of centromeric histone, Cse4, into the active genes in Δsan1. Collectively, our results demonstrate distinct functions of a nuclear protein quality control factor in regulating the genome-wide PIC formation and elongating Pol II (and hence transcription), thus unraveling new gene regulatory mechanisms.Keywords
Funding Information
- Foundation for the National Institutes of Health (2R15GM088798-03)
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