DSSR-PyMOL cartoon-block schematics: PDB entry 6vvj

PDB-id

6vvj; DSSR-derived features in text and JSON formats

Class

RNA

Method

NMR

Summary

Cap1g-tpua

Reference

Brown JD, Kharytonchyk S, Chaudry I, Iyer AS, Carter H, Becker G, Desai Y, Glang L, Choi SH, Singh K, Lopresti MW, Orellana M, Rodriguez T, Oboh U, Hijji J, Ghinger FG, Stewart K, Francis D, Edwards B, Chen P, Case DA, Telesnitsky A, Summers MF (2020): "Structural basis for transcriptional start site control of HIV-1 RNA fate." Science, 368, 413-417. doi: 10.1126/science.aaz7959.

Abstract

Heterogeneous transcriptional start site usage by HIV-1 produces 5'-capped RNAs beginning with one, two, or three 5'-guanosines (_Cap1G, _Cap2G, or _Cap3G, respectively) that are either selected for packaging as genomes (_Cap1G) or retained in cells as translatable messenger RNAs (mRNAs) (_Cap2G and _Cap3G). To understand how 5'-guanosine number influences fate, we probed the structures of capped HIV-1 leader RNAs by deuterium-edited nuclear magnetic resonance. The _Cap1G transcript adopts a dimeric multihairpin structure that sequesters the cap, inhibits interactions with eukaryotic translation initiation factor 4E, and resists decapping. The _Cap2G and _Cap3G transcripts adopt an alternate structure with an elongated central helix, exposed splice donor residues, and an accessible cap. Extensive remodeling, achieved at the energetic cost of a G-C base pair, explains how a single 5'-guanosine modifies the function of a ~9-kilobase HIV-1 transcript.