Title

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

GSBS Program

Biochemistry & Molecular Pharmacology

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Biochemistry and Molecular Pharmacology

Date

3-30-2001

Document Type

Article

Medical Subject Headings

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 Virus

Disciplines

Life Sciences | Medicine and Health Sciences

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 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.

Rights and Permissions

Citation: J Biol Chem. 2001 Apr 20;276(16):12959-66. Epub 2001 Jan 18. Link to article on publisher's site

Related Resources

Link to article in PubMed

PubMed ID

11278368