当前位置： SCI文献检索 > JOURNAL OF VIROLOGY期刊下所有文献 > Contributions of Individual Domains to Function of the HIV-1 Rev Response Element.

Contributions of Individual Domains to Function of the HIV-1 Rev Response Element.

Abstract：

:The HIV-1 Rev response element (RRE) is a 351-base element in unspliced and partially spliced viral RNA; binding of the RRE by the viral Rev protein induces nuclear export of RRE-containing RNAs, as required for virus replication. It contains one long, imperfect double helix (domain I), one branched domain (domain II) containing a high-affinity Rev-binding site, and two or three additional domains. We previously reported that the RRE assumes an "A" shape in solution and suggested that the location of the Rev binding sites in domains I and II, opposite each other on the two legs of the A, is optimal for Rev binding and explains Rev's specificity for RRE-containing RNAs. Using small-angle X-ray scattering (SAXS) and a quantitative functional assay, we have now analyzed a panel of RRE mutants. All the results support the essential role of the A shape for RRE function. Moreover, they suggest that the distal portion of domain I and the three crowning domains all contribute to the maintenance of the A shape. Domains I and II are necessary and sufficient for substantial RRE function, provided they are joined by a flexible linker that allows the two domains to face each other.IMPORTANCE Retroviral replication requires that some of the viral RNAs transcribed in the cell nucleus be exported to the cytoplasm without being spliced. To achieve this, HIV-1 encodes a protein, Rev, which binds to a complex, highly structured element within viral RNA, the Rev response element (RRE), and escorts RRE-containing RNAs from the nucleus. We previously reported that the RRE is "A" shaped and suggested that this architecture, with the 2 legs opposite one another, can explain the specificity of Rev for the RRE. We have analyzed the functional contributions of individual RRE domains and now report that several domains contribute, with some redundancy, to maintenance of the overall RRE shape. The data strongly support the hypothesis that the opposed placement of the 2 legs is essential for RRE function.

journal_name

J Virol

journal_title

Journal of virology

authors

O'Carroll IP,Thappeta Y,Fan L,Ramirez-Valdez EA,Smith S,Wang YX,Rein A

doi

10.1128/JVI.00746-17

subject

Has Abstract

pub_date

2017-10-13 00:00:00

issue

eissn

0022-538X

issn

1098-5514

pii

JVI.00746-17

journal_volume

pub_type

杂志文章

在线工具

Contributions of Individual Domains to Function of the HIV-1 Rev Response Element.