Preformed Protein-Binding Motifs in 7SK snRNA: Structural and Thermodynamic Comparisons with Retroviral TAR

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Preformed Protein-Binding Motifs in 7SK snRNA: Structural and Thermodynamic Comparisons with Retroviral TAR

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dc.contributor.author Durney, Michael Anthony
dc.contributor.author D'Souza, Victoria M.
dc.date.accessioned 2012-07-22T23:16:12Z
dc.date.issued 2010
dc.identifier.citation Durney, Michael Anthony, and Victoria M. D'Souza. 2010. Preformed protein-binding motifs in 7SK snRNA: Structural and thermodynamic comparisons with retroviral TAR. Journal of Molecular Biology 404(4): 555–567. en_US
dc.identifier.issn 0022-2836 en_US
dc.identifier.issn 1089-8638 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:9282599
dc.description.abstract The 7SK small nuclear RNA is a highly conserved non-coding RNA that regulates transcriptional elongation. 7SK utilizes the HEXIM proteins to sequester the transcription factor P-TEFb by a mechanism similar to that used by retroviral TAR RNA to engage Tat and P-TEFb. Tat has also recently been shown to bind 7SK directly and recruit P-TEFb to TAR. We report here the solution structures of the free and arginine-bound forms of stem loop 4 of 7SK (7SK-SL4). Comparison of the 7SK-SL4 and TAR structures demonstrates the presence of a common arginine sandwich motif. However, arginine binding to 7SK-SL4 is mechanistically distinct and occurs via docking into a pre-organized pocket resulting in a 1000-fold increased affinity. Furthermore, whereas formation of the binding pocket in TAR requires a critical base-triple, hydrogen-bond formation between the equivalent bases in 7SK-SL4 is not essential and the pocket is stabilized solely by a pseudo base-triple platform. In addition, this theme of preformed protein binding motifs also extends into the pentaloop. The configuration of the loop suggests that 7SK-SL4 is poised to make ternary contacts with P-TEFb and HEXIM or Tat. These key differences between 7SK-SL4 and TAR present an opportunity to understand RNA structural adaptation and have implications for understanding differential interactions with Tat. en_US
dc.description.sponsorship Molecular and Cellular Biology en_US
dc.language.iso en_US en_US
dc.publisher Elsevier en_US
dc.relation.isversionof doi:10.1016/j.jmb.2010.08.042 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pubmed/20816986 en_US
dash.license OAP
dc.subject elongation en_US
dc.subject 7SK en_US
dc.subject transactivation response region en_US
dc.subject equine infectious anemia virus en_US
dc.subject NMR en_US
dc.title Preformed Protein-Binding Motifs in 7SK snRNA: Structural and Thermodynamic Comparisons with Retroviral TAR en_US
dc.type Journal Article en_US
dc.description.version Author's Original en_US
dc.relation.journal Journal of Molecular Biology en_US
dash.depositing.author D'Souza, Victoria M.
dc.date.available 2012-07-22T23:16:12Z

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  • FAS Scholarly Articles [7106]
    Peer reviewed scholarly articles from the Faculty of Arts and Sciences of Harvard University

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