HIV-1 Tat protein interacts with mammalian capping enzyme and stimulates capping of TAR RNA Journal Article

  


Authors: Chiu, Y. L.; Coronel, E.; Ho, C. K.; Shuman, S.; Rana, T. M.
Article Title: HIV-1 Tat protein interacts with mammalian capping enzyme and stimulates capping of TAR RNA
Abstract: HIV gene expression is subject to a transcriptional checkpoint, whereby negative transcription elongation factors induce an elongation block that is overcome by HIV Tat protein in conjunction with P-TEFb. P-TEFb is a cyclin-dependent kinase that catalyzes Tat-dependent phosphorylation of Ser-5 of the Pol II C-terminal domain (CTD). Ser-5 phosphorylation confers on the CTD the ability to recruit the mammalian mRNA capping enzyme (Mce1) and stimulate its guanylyltransferase activity. Here we show that Tat spearheads a second and novel pathway of capping enzyme recruitment and activation via a direct physical interaction between the C-terminal domain of Tat and Mce1. Tat stimulates the guanylyl-transferase and triphosphatase activities of Mce1 and thereby enhances the otherwise low efficiency of cap formation on a TAR stem-loop RNA. Our findings suggest that multiple mechanisms exist for coupling transcription elongation and mRNA processing.
Keywords: protein phosphorylation; unclassified drug; genetics; nonhuman; protein domain; protein function; proteins; mouse; animal; metabolism; mammalia; animals; mice; gene expression; serine; carboxy terminal sequence; protein protein interaction; genetic transcription; enzyme activity; phosphorylation; rna; chemistry; kinetics; messenger rna; rna viruses; mammal; nucleotide sequence; transactivator protein; recombinant proteins; recombinant protein; base sequence; binding site; binding sites; human immunodeficiency virus; catalysis; enzyme kinetics; conformation; nucleic acid conformation; rna processing; cyclin dependent kinase; mammals; biochemistry; rna polymerase ii; enzyme mechanism; ribonucleases; human immunodeficiency virus 1; phosphoserine; catalyst activity; hiv-1; long terminal repeat; enzyme; elongation factor; nucleotidyltransferase; ribonuclease; rna capping; virus gene; nucleotidyltransferases; transferase; guanylyltransferase; capping enzyme; reaction kinetics; hiv long terminal repeat; virus transcription; messenger ribonucleic acid guanylyltransferase; humans; human; priority journal; article; gene products, tat; tar rna; mouse capping enzyme 1; protein p tefb
Journal Title: Journal of Biological Chemistry
Volume: 276
Issue: 16
ISSN: 0021-9258
Publisher: American Society for Biochemistry and Molecular Biology  
Date Published: 2001-04-20
Start Page: 12959
End Page: 12966
Language: English
DOI: 10.1074/jbc.M007901200
PUBMED: 11278368
PROVIDER: scopus
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-0035918271&partnerID=40&md5=affcc95844ba7f3dea8d8ca376145829
Notes: Export Date: 21 May 2015 -- Source: Scopus
Altmetric
What is Altmetric?
Citation Impact
What is Dimensions Citation Badge?
BMJ Impact Analytics
MSK Authors
  1. Chong-Kiong Ho
    33 Ho
  2. Stewart H Shuman
    546 Shuman
Related MSK Work