Ssl2/TFIIH function in transcription start site scanning by RNA polymerase II in Saccharomyces cerevisiae

In Saccharomyces cerevisiae, RNA polymerase II (Pol II) selects transcription start sites (TSSs) by a unidirectional scanning process. During scanning, a preinitiation complex (PIC) assembled at an upstream core promoter initiates at select positions within a window ~40–120 bp downstream. Several li...

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Autores principales:	Tingting Zhao, Irina O Vvedenskaya, William KM Lai, Shrabani Basu, B Franklin Pugh, Bryce E Nickels, Craig D Kaplan
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	transcription initiation RNA polymerase II yeast general transcription factors transcription start site Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/37c27916ae4b45b0b114094caef6209f
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spelling	oai:doaj.org-article:37c27916ae4b45b0b114094caef6209f2021-11-12T15:34:05ZSsl2/TFIIH function in transcription start site scanning by RNA polymerase II in Saccharomyces cerevisiae10.7554/eLife.710132050-084Xe71013https://doaj.org/article/37c27916ae4b45b0b114094caef6209f2021-10-01T00:00:00Zhttps://elifesciences.org/articles/71013https://doaj.org/toc/2050-084XIn Saccharomyces cerevisiae, RNA polymerase II (Pol II) selects transcription start sites (TSSs) by a unidirectional scanning process. During scanning, a preinitiation complex (PIC) assembled at an upstream core promoter initiates at select positions within a window ~40–120 bp downstream. Several lines of evidence indicate that Ssl2, the yeast homolog of XPB and an essential and conserved subunit of the general transcription factor (GTF) TFIIH, drives scanning through its DNA-dependent ATPase activity, therefore potentially controlling both scanning rate and scanning extent (processivity). To address questions of how Ssl2 functions in promoter scanning and interacts with other initiation activities, we leveraged distinct initiation-sensitive reporters to identify novel ssl2 alleles. These ssl2 alleles, many of which alter residues conserved from yeast to human, confer either upstream or downstream TSS shifts at the model promoter ADH1 and genome-wide. Specifically, tested ssl2 alleles alter TSS selection by increasing or narrowing the distribution of TSSs used at individual promoters. Genetic interactions of ssl2 alleles with other initiation factors are consistent with ssl2 allele classes functioning through increasing or decreasing scanning processivity but not necessarily scanning rate. These alleles underpin a residue interaction network that likely modulates Ssl2 activity and TFIIH function in promoter scanning. We propose that the outcome of promoter scanning is determined by two functional networks, the first being Pol II activity and factors that modulate it to determine initiation efficiency within a scanning window, and the second being Ssl2/TFIIH and factors that modulate scanning processivity to determine the width of the scanning widow.Tingting ZhaoIrina O VvedenskayaWilliam KM LaiShrabani BasuB Franklin PughBryce E NickelsCraig D KaplaneLife Sciences Publications Ltdarticletranscription initiationRNA polymerase IIyeastgeneral transcription factorstranscription start siteMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	transcription initiation RNA polymerase II yeast general transcription factors transcription start site Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	transcription initiation RNA polymerase II yeast general transcription factors transcription start site Medicine R Science Q Biology (General) QH301-705.5 Tingting Zhao Irina O Vvedenskaya William KM Lai Shrabani Basu B Franklin Pugh Bryce E Nickels Craig D Kaplan Ssl2/TFIIH function in transcription start site scanning by RNA polymerase II in Saccharomyces cerevisiae
description	In Saccharomyces cerevisiae, RNA polymerase II (Pol II) selects transcription start sites (TSSs) by a unidirectional scanning process. During scanning, a preinitiation complex (PIC) assembled at an upstream core promoter initiates at select positions within a window ~40–120 bp downstream. Several lines of evidence indicate that Ssl2, the yeast homolog of XPB and an essential and conserved subunit of the general transcription factor (GTF) TFIIH, drives scanning through its DNA-dependent ATPase activity, therefore potentially controlling both scanning rate and scanning extent (processivity). To address questions of how Ssl2 functions in promoter scanning and interacts with other initiation activities, we leveraged distinct initiation-sensitive reporters to identify novel ssl2 alleles. These ssl2 alleles, many of which alter residues conserved from yeast to human, confer either upstream or downstream TSS shifts at the model promoter ADH1 and genome-wide. Specifically, tested ssl2 alleles alter TSS selection by increasing or narrowing the distribution of TSSs used at individual promoters. Genetic interactions of ssl2 alleles with other initiation factors are consistent with ssl2 allele classes functioning through increasing or decreasing scanning processivity but not necessarily scanning rate. These alleles underpin a residue interaction network that likely modulates Ssl2 activity and TFIIH function in promoter scanning. We propose that the outcome of promoter scanning is determined by two functional networks, the first being Pol II activity and factors that modulate it to determine initiation efficiency within a scanning window, and the second being Ssl2/TFIIH and factors that modulate scanning processivity to determine the width of the scanning widow.
format	article
author	Tingting Zhao Irina O Vvedenskaya William KM Lai Shrabani Basu B Franklin Pugh Bryce E Nickels Craig D Kaplan
author_facet	Tingting Zhao Irina O Vvedenskaya William KM Lai Shrabani Basu B Franklin Pugh Bryce E Nickels Craig D Kaplan
author_sort	Tingting Zhao
title	Ssl2/TFIIH function in transcription start site scanning by RNA polymerase II in Saccharomyces cerevisiae
title_short	Ssl2/TFIIH function in transcription start site scanning by RNA polymerase II in Saccharomyces cerevisiae
title_full	Ssl2/TFIIH function in transcription start site scanning by RNA polymerase II in Saccharomyces cerevisiae
title_fullStr	Ssl2/TFIIH function in transcription start site scanning by RNA polymerase II in Saccharomyces cerevisiae
title_full_unstemmed	Ssl2/TFIIH function in transcription start site scanning by RNA polymerase II in Saccharomyces cerevisiae
title_sort	ssl2/tfiih function in transcription start site scanning by rna polymerase ii in saccharomyces cerevisiae
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/37c27916ae4b45b0b114094caef6209f
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Ssl2/TFIIH function in transcription start site scanning by RNA polymerase II in Saccharomyces cerevisiae

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