title: Pseudouridylation of 7SK snRNA promotes 7SK snRNP formation to suppress HIV-1 transcription and escape from latency.
abstract: The 7SK snRNA sequesters P-TEFb, a general transcription elongation factor and human co-factor for HIV-1 Tat protein, into the catalytically inactive 7SK snRNP Little is known about how 7SK RNA is regulated to perform this function. Here, we show that most of 7SK is pseudouridylated at position U250 by the predominant cellular pseudouridine synthase machinery, the DKC1-box H/ACA RNP Pseudouridylation is critical to stabilize 7SK snRNP, as its abolishment by either mutation at or around U250 or depletion of DKC1, the catalytic component of the box H/ACA RNP, disrupts 7SK snRNP and releases P-TEFb to form the super elongation complex (SEC) and the Brd4-P-TEFb complex. The SEC is then recruited by Tat to the HIV-1 promoter to stimulate viral transcription and escape from latency. Thus, although 7SK RNA levels remain mostly unchanged, its function is modulated by pseudouridylation, which in turn controls transcription of both HIV-1 and cellular genes.
authors: Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
authors: Yang
authors: Y
authors: Zhao
authors: Department of Plant and Microbial Biology, University of California, Berkeley, CA, USA.
authors: John
authors: J
authors: Karijolich
authors: Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA Department of Plant and Microbial Biology, University of California, Berkeley, CA, USA Howard Hughes Medical Institute, University of California, Berkeley, CA, USA.
authors: Britt
authors: B
authors: Glaunsinger
authors: Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA qzhou@berkeley.edu.
authors: Qiang
authors: 0000-0001-7202-3947
authors: Q
authors: Zhou
mesh_terms: D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D015658:HIV Infections / Q000378:metabolism* / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism; D009690:Nucleic Acid Conformation; D042925:Positive Transcriptional Elongation Factor B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D062085:RNA, Long Noncoding / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017411:Ribonucleoproteins, Small Nuclear / Q000378:metabolism*; D014158:Transcription, Genetic; D017735:Virus Latency
chemical_list: D018797:Cell Cycle Proteins; C112148:DKC1 protein, human; D009687:Nuclear Proteins; D062085:RNA, Long Noncoding; D017411:Ribonucleoproteins, Small Nuclear; C000610089:long non-coding RNA 7SK, human; D042925:Positive Transcriptional Elongation Factor B
keywords: 7SK snRNA; HIV‐1 transcription; P‐TEFb; latency; pseudouridylation