The chaperone protein p32 stabilizes HIV-1 Tat and strengthens the p-TEFb/RNAPII/TAR complex promoting HIV transcription elongation.
Humans
Positive Transcriptional Elongation Factor B
/ genetics
HIV-1
/ physiology
tat Gene Products, Human Immunodeficiency Virus
/ genetics
Transcription Factors
/ genetics
RNA Polymerase II
/ genetics
Molecular Chaperones
/ metabolism
HIV Infections
/ genetics
Transcription, Genetic
HIV Long Terminal Repeat
/ genetics
HIV
Tat
p32
regulation
transcription
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
03 01 2023
03 01 2023
Historique:
entrez:
30
12
2022
pubmed:
31
12
2022
medline:
4
1
2023
Statut:
ppublish
Résumé
HIV gene expression is modulated by the combinatorial activity of the HIV transcriptional activator, Tat, host transcription factors, and chromatin remodeling complexes. To identify host factors regulating HIV transcription, we used specific single-guide RNAs and endonuclease-deficient Cas9 to perform chromatin affinity purification of the integrated HIV promoter followed by mass spectrometry. The scaffold protein, p32, also called ASF/SF2 splicing factor-associated protein, was identified among the top enriched factors present in actively transcribing HIV promoters but absent in silenced ones. Chromatin immunoprecipitation analysis confirmed the presence of p32 on active HIV promoters and its enhanced recruitment by Tat. HIV uses Tat to efficiently recruit positive transcription elongation factor b (p-TEFb) (CDK9/CCNT1) to TAR, an RNA secondary structure that forms from the first 59 bp of HIV transcripts, to enhance RNAPII transcriptional elongation. The RNA interference of p32 significantly reduced HIV transcription in primary CD4
Identifiants
pubmed: 36584296
doi: 10.1073/pnas.2217476120
pmc: PMC9910500
doi:
Substances chimiques
Positive Transcriptional Elongation Factor B
EC 2.7.11.-
tat Gene Products, Human Immunodeficiency Virus
0
Transcription Factors
0
RNA Polymerase II
EC 2.7.7.-
Molecular Chaperones
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2217476120Subventions
Organisme : NIAID NIH HHS
ID : R33 AI140439
Pays : United States
Organisme : NIAID NIH HHS
ID : R37 AI165137
Pays : United States
Organisme : NIAID NIH HHS
ID : R61 AI140439
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI164559
Pays : United States
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