HIV-1 Tat protein interacts with mammalian capping enzyme and stimulates capping of TAR RNA
UMass Chan Affiliations
Department of Biochemistry and Molecular PharmacologyGraduate School of Biomedical Sciences
Document Type
Journal ArticlePublication Date
2001-03-30Keywords
Animals; Base Sequence; Binding Sites; Gene Products, tat; HIV Long Terminal Repeat; HIV-1; Humans; Kinetics; Mammals; Mice; Nucleic Acid Conformation; Nucleotidyltransferases; Phosphorylation; Phosphoserine; RNA Polymerase II; Recombinant Proteins; Ribonucleases; tat Gene Products, Human Immunodeficiency VirusLife Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
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 guanylyltransferase 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.Source
J Biol Chem. 2001 Apr 20;276(16):12959-66. Epub 2001 Jan 18. Link to article on publisher's siteDOI
10.1074/jbc.M007901200Permanent Link to this Item
http://hdl.handle.net/20.500.14038/33538PubMed ID
11278368Related Resources
Link to article in PubMedae974a485f413a2113503eed53cd6c53
10.1074/jbc.M007901200