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
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.