Analysis of the interaction with the hepatitis C virus mRNA reveals an alternative mode of RNA recognition by the human La protein.

Abstract:

:Human La protein is an essential factor in the biology of both coding and non-coding RNAs. In the nucleus, La binds primarily to 3' oligoU containing RNAs, while in the cytoplasm La interacts with an array of different mRNAs lacking a 3' UUU(OH) trailer. An example of the latter is the binding of La to the IRES domain IV of the hepatitis C virus (HCV) RNA, which is associated with viral translation stimulation. By systematic biophysical investigations, we have found that La binds to domain IV using an RNA recognition that is quite distinct from its mode of binding to RNAs with a 3' UUU(OH) trailer: although the La motif and first RNA recognition motif (RRM1) are sufficient for high-affinity binding to 3' oligoU, recognition of HCV domain IV requires the La motif and RRM1 to work in concert with the atypical RRM2 which has not previously been shown to have a significant role in RNA binding. This new mode of binding does not appear sequence specific, but recognizes structural features of the RNA, in particular a double-stranded stem flanked by single-stranded extensions. These findings pave the way for a better understanding of the role of La in viral translation initiation.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Martino L,Pennell S,Kelly G,Bui TT,Kotik-Kogan O,Smerdon SJ,Drake AF,Curry S,Conte MR

doi

10.1093/nar/gkr890

subject

Has Abstract

pub_date

2012-02-01 00:00:00

pages

1381-94

issue

3

eissn

0305-1048

issn

1362-4962

pii

gkr890

journal_volume

40

pub_type

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