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

Citation
Yl. Chiu et al., HIV-1 Tat protein interacts with mammalian capping enzyme and stimulates capping of TAR RNA, J BIOL CHEM, 276(16), 2001, pp. 12959-12966
Citations number
46
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
00219258 → ACNP
Volume
276
Issue
16
Year of publication
2001
Pages
12959 - 12966
Database
ISI
SICI code
0021-9258(20010420)276:16<12959:HTPIWM>2.0.ZU;2-X
Abstract
HIV gene expression is subject to a transcriptional checkpoint, whereby neg ative transcription elongation factors induce an elongation block that is o vercome by HIV Tat protein in conjunction with P-TEFb. P-TEFb is a cyclin d ependent kinase that catalyzes Tat-dependent phosphorylation of Ser-5 of th e Pol II C-terminal domain (CTD). Ser-5 phosphorylation confers on the CTD the ability to recruit the mammalian mRNA capping enzyme (Mcel) and stimula te its guanylyltransferase activity. Here we show that Tat spearheads a sec ond and novel pathway of capping enzyme recruitment and activation via a di rect physical interaction between the C-terminal domain of Tat and Mcel. Ta t stimulates the guanylyl transferase and triphosphatase activities of Mcel and thereby enhances the otherwise low efficiency of cap formation on a TA R stem-loop RNA. Our findings suggest that multiple mechanisms exist for co upling transcription elongation and mRNA processing.