Preformed Protein-Binding Motifs in 7SK snRNA: Structural and Thermodynamic Comparisons with Retroviral TAR
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| dc.contributor.author |
Durney, Michael Anthony
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| dc.contributor.author |
D'Souza, Victoria M.
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| dc.date.accessioned |
2012-07-22T23:16:12Z |
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| dc.date.issued |
2010 |
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| 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 |
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| 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 |
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| dc.language.iso |
en_US |
en_US |
| dc.publisher |
Elsevier |
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| 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 |
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| dc.subject |
elongation |
en_US |
| dc.subject |
7SK |
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| dc.subject |
transactivation response region |
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| 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 [5128]
Peer reviewed scholarly articles from the Faculty of Arts and Sciences of Harvard University
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