Genome-Wide Regulations of the Preinitiation Complex Formation and Elongating RNA Polymerase II by an E3 Ubiquitin Ligase, San1

• Published in: Molecular and cellular biology 2022-01, Vol.42 (1), p.e0036821-e0036821
• Main Authors: Barman, Priyanka, Sen, Rwik, Kaja, Amala, Ferdoush, Jannatul, Guha, Shalini, Govind, Chhabi K., Bhaumik, Sukesh R.
• Format: Article
• Language: English
• Subjects: ChIP-seq; DNA-Binding Proteins - metabolism; Genetics and Molecular Biology; Genome-Wide Association Study - methods; Nuclear Proteins - metabolism; Promoter Regions, Genetic - genetics; Research Article; RNA polymerase II; RNA Polymerase II - metabolism; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - metabolism; San1; TBP; transcription; Transcription Factors - metabolism; Ubiquitin - metabolism; Ubiquitin-Protein Ligases - metabolism
• ISSN: 0270-7306; 1098-5549; 1098-5549
• DOI: 10.1128/MCB.00368-21

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 the genome-wide association of TATA box binding protein (TBP; which nucleates preinitiation 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 the Δsan1 strain. 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.