PUBLICATION

Regulation of polymerase II transcription by 7SK snRNA: two distinct RNA elements direct P-TEFb and HEXIM1 binding

Authors
Egloff, S., Van Herreweghe, E., and Kiss, T.
ID
ZDB-PUB-090318-1
Date
2006
Source
Molecular and cellular biology   26(2): 630-642 (Journal)
Registered Authors
Keywords
none
MeSH Terms
  • 3' Flanking Region
  • 5' Flanking Region
  • Base Sequence
  • Cell Line
  • Conserved Sequence
  • Humans
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • Phosphorylation
  • Positive Transcriptional Elongation Factor B/genetics
  • Positive Transcriptional Elongation Factor B/metabolism*
  • Protein Binding
  • RNA Polymerase II/genetics
  • RNA Polymerase II/metabolism*
  • RNA, Small Nuclear/genetics*
  • RNA-Binding Proteins/genetics
  • RNA-Binding Proteins/metabolism*
  • Transcriptional Activation*
PubMed
16382153 Full text @ Mol. Cell. Biol.
Abstract
The positive transcription elongation factor b (P-TEFb), a complex of Cdk9 and cyclin T1/T2, stimulates transcription by phosphorylating RNA polymerase II. The 7SK small nuclear RNA, in cooperation with HEXIM1 protein, functions as a general polymerase II transcription regulator by sequestering P-TEFb into a large kinase-inactive 7SK/HEXIM1/P-TEFb complex. Here, determination and characterization of the functionally essential elements of human 7SK snRNA directing HEXIM1 and P-TEFb binding led to a new model for the assembly of the 7SK/HEXIM1/P-TEFb regulatory complex. We demonstrate that two structurally and functionally distinct protein binding elements located in the 5'- and 3'-terminal hairpins of 7SK support the in vivo recruitment of HEXIM1 and P-TEFb. Consistently, a minimal regulatory RNA composed of the 5' and 3' hairpins of 7SK can modulate polymerase II transcription in HeLa cells. HEXIM1 binds independently and specifically to the G24-C48/G60-C87 distal segment of the 5' hairpin of 7SK. Binding of HEXIM1 is a prerequisite for association of P-TEFb with the G302-C324 apical region of the 3' hairpin of 7SK that is highly reminiscent of the human immunodeficiency virus transactivation-responsive RNA.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping