Rosamaria Y. Moreno, Svetlana B. Panina, Seema Irani, Haley A. Hardtke, Renee Stephenson, Brendan M. Floyd, Edward M. Marcotte, Qian Zhang, Y. Jessie Zhang
{"title":"RNA Pol II 上的 Thr4 磷酸化发生在调节 3'-end 处理的转录早期。","authors":"Rosamaria Y. Moreno, Svetlana B. Panina, Seema Irani, Haley A. Hardtke, Renee Stephenson, Brendan M. Floyd, Edward M. Marcotte, Qian Zhang, Y. Jessie Zhang","doi":"10.1126/sciadv.adq0350","DOIUrl":null,"url":null,"abstract":"<div >RNA polymerase II relies on a repetitive sequence domain (YSPTSPS) within its largest subunit to orchestrate transcription. While phosphorylation on serine-2/serine-5 of the carboxyl-terminal heptad repeats is well established, threonine-4’s role remains enigmatic. Paradoxically, threonine-4 phosphorylation was only detected after transcription end sites despite functionally implicated in pausing, elongation, termination, and messenger RNA processing. Our investigation revealed that threonine-4 phosphorylation detection was obstructed by flanking serine-5 phosphorylation at the onset of transcription, which can be removed selectively. Subsequent proteomic analyses identified many proteins recruited to transcription via threonine-4 phosphorylation, which previously were attributed to serine-2. Loss of threonine-4 phosphorylation greatly reduces serine-2 phosphorylation, revealing a cross-talk between the two marks. Last, the function analysis of the threonine-4 phosphorylation highlighted its role in alternative 3′-end processing within pro-proliferative genes. Our findings unveil the true genomic location of this evolutionarily conserved phosphorylation mark and prompt a reassessment of functional assignments of the carboxyl-terminal domain.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":null,"pages":null},"PeriodicalIF":11.7000,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adq0350","citationCount":"0","resultStr":"{\"title\":\"Thr4 phosphorylation on RNA Pol II occurs at early transcription regulating 3′-end processing\",\"authors\":\"Rosamaria Y. Moreno, Svetlana B. Panina, Seema Irani, Haley A. Hardtke, Renee Stephenson, Brendan M. Floyd, Edward M. Marcotte, Qian Zhang, Y. Jessie Zhang\",\"doi\":\"10.1126/sciadv.adq0350\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div >RNA polymerase II relies on a repetitive sequence domain (YSPTSPS) within its largest subunit to orchestrate transcription. While phosphorylation on serine-2/serine-5 of the carboxyl-terminal heptad repeats is well established, threonine-4’s role remains enigmatic. Paradoxically, threonine-4 phosphorylation was only detected after transcription end sites despite functionally implicated in pausing, elongation, termination, and messenger RNA processing. Our investigation revealed that threonine-4 phosphorylation detection was obstructed by flanking serine-5 phosphorylation at the onset of transcription, which can be removed selectively. Subsequent proteomic analyses identified many proteins recruited to transcription via threonine-4 phosphorylation, which previously were attributed to serine-2. Loss of threonine-4 phosphorylation greatly reduces serine-2 phosphorylation, revealing a cross-talk between the two marks. Last, the function analysis of the threonine-4 phosphorylation highlighted its role in alternative 3′-end processing within pro-proliferative genes. Our findings unveil the true genomic location of this evolutionarily conserved phosphorylation mark and prompt a reassessment of functional assignments of the carboxyl-terminal domain.</div>\",\"PeriodicalId\":21609,\"journal\":{\"name\":\"Science Advances\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":11.7000,\"publicationDate\":\"2024-09-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.science.org/doi/reader/10.1126/sciadv.adq0350\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Science Advances\",\"FirstCategoryId\":\"103\",\"ListUrlMain\":\"https://www.science.org/doi/10.1126/sciadv.adq0350\",\"RegionNum\":1,\"RegionCategory\":\"综合性期刊\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MULTIDISCIPLINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Science Advances","FirstCategoryId":"103","ListUrlMain":"https://www.science.org/doi/10.1126/sciadv.adq0350","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
Thr4 phosphorylation on RNA Pol II occurs at early transcription regulating 3′-end processing
RNA polymerase II relies on a repetitive sequence domain (YSPTSPS) within its largest subunit to orchestrate transcription. While phosphorylation on serine-2/serine-5 of the carboxyl-terminal heptad repeats is well established, threonine-4’s role remains enigmatic. Paradoxically, threonine-4 phosphorylation was only detected after transcription end sites despite functionally implicated in pausing, elongation, termination, and messenger RNA processing. Our investigation revealed that threonine-4 phosphorylation detection was obstructed by flanking serine-5 phosphorylation at the onset of transcription, which can be removed selectively. Subsequent proteomic analyses identified many proteins recruited to transcription via threonine-4 phosphorylation, which previously were attributed to serine-2. Loss of threonine-4 phosphorylation greatly reduces serine-2 phosphorylation, revealing a cross-talk between the two marks. Last, the function analysis of the threonine-4 phosphorylation highlighted its role in alternative 3′-end processing within pro-proliferative genes. Our findings unveil the true genomic location of this evolutionarily conserved phosphorylation mark and prompt a reassessment of functional assignments of the carboxyl-terminal domain.
期刊介绍:
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