A structure-based mechanism for tRNA and retroviral RNA remodelling during primer annealing

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A structure-based mechanism for tRNA and retroviral RNA remodelling during primer annealing

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Title: A structure-based mechanism for tRNA and retroviral RNA remodelling during primer annealing
Author: Miller, Sarah; Yildiz, Fatma Zehra; Lo, Jennifer Alys; Wang, Bo; D'Souza, Victoria M

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Citation: Miller, Sarah B., F. Zehra Yildiz, Jennifer A. Lo, Bo Wang, and Victoria M. D’Souza. 2014. “A Structure-Based Mechanism for tRNA and Retroviral RNA Remodelling During Primer Annealing.” Nature 515 (7528) (September 7): 591–595. doi:10.1038/nature13709.
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Abstract: To prime reverse transcription, retroviruses require annealing of a transfer RNA molecule to the U5 primer binding site (U5-PBS) region of the viral genome [1,2]. The residues essential for primer annealing are initially locked in intramolecular interactions [3,4,5]; hence, annealing requires the chaperone activity of the retroviral nucleocapsid (NC) protein to facilitate structural rearrangements [6]. Here we show that, unlike classical chaperones, the Moloney murine leukaemia virus NC uses a unique mechanism for remodelling: it specifically targets multiple structured regions in both the U5-PBS and \(tRNA^{Pro}\) primer that otherwise sequester residues necessary for annealing. This high-specificity and high-affinity binding by NC consequently liberates these sequestered residues—which are exactly complementary—for intermolecular interactions. Furthermore, NC utilizes a step-wise, entropy-driven mechanism to trigger both residue-specific destabilization and residue-specific release. Our structures of NC bound to U5-PBS and tRNA^{Pro} reveal the structure-based mechanism for retroviral primer annealing and provide insights as to how ATP-independent chaperones can target specific RNAs amidst the cellular milieu of non-target RNAs.
Published Version: doi:10.1038/nature13709
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:25975321
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