Linked Life Data

19508234

Source:http://linkedlifedata.com/resource/pubmed/id/19508234

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2009-8-11
pubmed:abstractText
Small RNAs modulate gene expression by forming a ribonucleoprotein complex with Argonaute proteins and directing them to specific complementary sites in target nucleic acids. However, the interactions required for the recruitment of the target nucleic acid to the ribonucleoprotein complex are poorly understood. In the present manuscript we have investigated this question by using let-7a, Argonaute2 and a fully complementary mRNA target. Importantly, we have found that recombinant Argonaute2 is sufficient to direct let-7a guided cleavage of mRNA. Thus this model system has allowed us to investigate the mechanistic basis of silencing in vitro and in vivo. Current models suggest that Argonaute proteins bind to both the 5' and 3' termini of the guide RNA. We have found that the termini of the let-7a microRNA are indeed critical, since circular let-7a does not support mRNA cleavage. However, the 5' end is the key determinant, since its deletion abrogates activity. Surprisingly, we have found that alteration of the 5' terminal uracil compromises mRNA cleavage. Importantly, we have found that substitution of this base has little effect upon the formation of the binary let-7a-Argonaute2 complex, but inhibits the formation of the ternary let-7a-Argonaute2-mRNA complex. Thus we conclude that the interaction of the 5' uracil base with Argonaute2 plays a critical and novel role in the recruitment of mRNA.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1470-8728
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
422
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
329-41
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
The 5' terminal uracil of let-7a is critical for the recruitment of mRNA to Argonaute2.
pubmed:affiliation
Department of Molecular, Microbial and Structural Biology and Graduate Program in Molecular Biology and Biochemistry, University of Connecticut Health Center, Farmington, CT 06030, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, N.I.H., Extramural