HIV-1 Tat protein interacts with mammalian capping enzyme and stimulates capping of TAR RNA
Biochemistry & Molecular Pharmacology
Graduate School of Biomedical Sciences; Department of Biochemistry and Molecular Pharmacology
Life Sciences | Medicine and Health Sciences
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.
DOI of Published Version
J Biol Chem. 2001 Apr 20;276(16):12959-66. Epub 2001 Jan 18. Link to article on publisher's site
The Journal of biological chemistry
Chiu, Ya-Lin; Coronel, Elizabeth; Ho, C. Kiong; Shuman, Stewart; and Rana, Tariq M., "HIV-1 Tat protein interacts with mammalian capping enzyme and stimulates capping of TAR RNA" (2001). GSBS Student Publications. 210.