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New insights into the control of HIV-1 transcription: when Tat meets the 7SK snRNP and super elongation complex (SEC).

Abstract
Recent studies aimed at elucidating the mechanism controlling HIV-1 transcription have led to the identification and characterization of two multi-subunit complexes that both contain P-TEFb, a human transcription elongation factor and co-factor for activation of HIV-1 gene expression by the viral Tat protein. The first complex, termed the 7SK snRNP, acts as a reservoir where active P-TEFb can be withdrawn by Tat to stimulate HIV-1 transcription. The second complex, termed the super elongation complex (SEC), represents the form of P-TEFb delivered by Tat to the paused RNA polymerase II at the viral long terminal repeat during Tat transactivation. Besides P-TEFb, SEC also contains other elongation factors/co-activators, and they cooperatively stimulate HIV-1 transcription. Recent data also indicate SEC as a target for the mixed lineage leukemia (MLL) protein to promote the expression of MLL target genes and leukemogenesis. Given their roles in HIV-1/AIDS and cancer, further characterization of 7SK snRNP and SEC will help develop strategies to suppress aberrant transcriptional elongation caused by uncontrolled P-TEFb activation. As both complexes are also important for normal cellular gene expression, studying their structures and functions will elucidate the mechanisms that control metazoan transcriptional elongation in general.
AuthorsNanhai He, Qiang Zhou
JournalJournal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology (J Neuroimmune Pharmacol) Vol. 6 Issue 2 Pg. 260-8 (Jun 2011) ISSN: 1557-1904 [Electronic] United States
PMID21360054 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
Chemical References
  • Ribonucleoproteins, Small Nuclear
  • tat Gene Products, Human Immunodeficiency Virus
  • Positive Transcriptional Elongation Factor B
Topics
  • Animals
  • HIV-1 (genetics, metabolism)
  • Humans
  • Positive Transcriptional Elongation Factor B (genetics, metabolism)
  • Ribonucleoproteins, Small Nuclear (genetics, metabolism)
  • Transcription, Genetic (physiology)
  • tat Gene Products, Human Immunodeficiency Virus (genetics, metabolism)

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