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Heterogeneous structures formed by conserved RNA sequences within the HIV reverse transcription initiation site.

Heterogeneous structures formed by conserved RNA sequences within the HIV reverse transcription initiation site.
Author Information (click to view)

Coey A, Larsen K, Puglisi JD, Puglisi EV,


Coey A, Larsen K, Puglisi JD, Puglisi EV, (click to view)

Coey A, Larsen K, Puglisi JD, Puglisi EV,

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RNA (New York, N.Y.) 2016 9 9()

Abstract

Reverse transcription is a key process in the early steps of HIV infection. This process initiates within a specific complex formed by the 5′ UTR of the HIV genomic RNA (vRNA) and a host primer tRNA(Lys) 3 Using nuclear magnetic resonance (NMR) spectroscopy and single-molecule fluorescence spectroscopy, we detect two distinct conformers adopted by the tRNA/vRNA initiation complex. We directly show that an interaction between the conserved 8-nucleotide viral RNA primer activation signal (PAS) and the primer tRNA occurs in one of these conformers. This intermolecular PAS interaction likely induces strain on a vRNA intramolecular helix, which must be broken for reverse transcription to initiate. We propose a mechanism by which this vRNA/tRNA conformer relieves the kinetic block formed by the vRNA intramolecular helix to initiate reverse transcription.

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