Rana TM, Huq I, Ping YH; Keystone Symposia on Molecular and Cellular Biology: 1998 HIV Pathogenesis and Treatment.
Keyst Symp Mol Cell Biol Keyst Symp Mol Cell Biol. 1998 Mar 13-19; 43 (abstract no. 1018).
Department of Pharmacology, Robert Wood Johnson Medical School, Piscataway, NJ.
Small unnatural peptides that target specific RNA structures have the potential to control biological processes. RNA-protein interactions are important in many cellular functions, including transcription, RNA splicing, and translation. One example of such interactions is the mechanism of trans-activation of human immunodeficiency virus type 1 (HIV-1) gene expression that requires the interaction of Tat protein with the trans-activation responsive region (TAR) RNA, a 59-bases stem-loop structure located at the 5'-end of all nascent HIV-1 transcripts. We designed two unnatural peptides containing the basic-arginine rich region of Tat, and tested for TAR RNA binding. This tat-derived unnatural biopolymers can specifically bind TAR RNA with high affinities (Wang et al., J. Am. Chem. Soc. 1997, 119, 6444; Huq et al., Nature Str. Biol. 1997, 4, 881). Site-specific photocrosslinking experiments using a photoactive analog (4-thio-uracil) containing TAR RNA revealed that the unnatural biopolymers interact with RNA in the major groove. We report here a synthetic peptide derived from Tat sequence (37-72) containing all D-amino acids which binds in the major groove of TAR RNA and interferes with transcriptional activation by Tat protein in vitro and in HeLa cells. Our results indicate that unnatural peptides can inhibit the transcription of specific genes regulated by RNA-protein interactions.
Publication Types:
Keywords:
- Base Sequence
- Gene Products, tat
- Genes, tat
- HIV-1
- Hela Cells
- Humans
- In Vitro
- Peptides
- Protein Biosynthesis
- RNA
- RNA Polymerase II
- RNA-Binding Proteins
- Trans-Activation (Genetics)
- genetics
Other ID:
UI: 102236704
From Meeting Abstracts