Structural basis for transcriptional start site control of HIV-1 RNA fate.
basic_science · Level V
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- Record sourced from PubMed, PMID 32327595.
- Also identified by DOI 10.1126/science.aaz7959 and PMC identifier 7351118.
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Abstract
Heterogeneous transcriptional start site usage by HIV-1 produces 5'-capped RNAs beginning with one, two, or three 5'-guanosines (<sup>Cap</sup>1G, <sup>Cap</sup>2G, or <sup>Cap</sup>3G, respectively) that are either selected for packaging as genomes (<sup>Cap</sup>1G) or retained in cells as translatable messenger RNAs (mRNAs) (<sup>Cap</sup>2G and <sup>Cap</sup>3G). 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 <sup>Cap</sup>1G transcript adopts a dimeric multihairpin structure that sequesters the cap, inhibits interactions with eukaryotic translation initiation factor 4E, and resists decapping. The <sup>Cap</sup>2G and <sup>Cap</sup>3G 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.
Medical subject headings
- Base Pairing
- Gene Expression Regulation, Viral
- HIV-1
- RNA Caps
- RNA, Viral
- Transcription Initiation Site