Evidence map›Paper›PMID 19508234›Full record

ArticleThe Biochemical journal2009

The 5' terminal uracil of let-7a is critical for the recruitment of mRNA to Argonaute2.

Kristin M Felice, David W Salzman, Jonathan Shubert-Coleman, Kevin P Jensen, Henry M Furneaux

Open access · greenAbstract readComparative Study
In one paragraph

Article in The Biochemical journal, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.1field-weighted citation impact, top 23% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 36 citations in OpenAlex.

  1. Article
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  4. Article
  5. Conformational Dynamics of Ago-Mediated Silencing Processes.International journal of molecular sciences · 2015
    Review
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  15. Uridylation of mature miRNAs and siRNAs by the MUT68 nucleotidyltransferase promotes their degradation in Chlamydomonas.Proceedings of the National Academy of Sciences of the United States of America · 2010
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Kristin M FeliceDepartment of Molecular, Microbial and Structural Biology and Graduate Program in Molecular Biology and Biochemistry, University of Connecticut Health Center, Farmington, CT 06030, USA.
David W Salzman
Jonathan Shubert-Coleman
Kevin P Jensen
Henry M Furneaux
UConn Health · US

Funding

Vascular Pathophysiology and History Core (VPHC)P01HL070694 · NHLBI · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI COWAN, ANN E. · 2002 to 2013
$17.5M
Cannabinoid Receptor (CNR1) MicroRNAs and Addictive DiseaseR03DA022226 · NIDA · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI FURNEAUX, HENRY M · 2006 to 2007
$292k
NHLBI NIH HHS P01 HL070694NHLBI NIH HHS P01HL70694NIDA NIH HHS R03 DA022226
6 · The paper itself

Abstract

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.

Indexed as

5' Untranslated RegionsArgonaute ProteinsConserved SequenceEukaryotic Initiation Factor-2HeLa CellsHumansMicroRNAsProtein Structure, TertiaryRibonucleoproteinsRNA, MessengerRNA, Small UntranslatedUracil5' Untranslated RegionsAGO2 protein, humanArgonaute ProteinsEukaryotic Initiation Factor-2MicroRNAsmirnlet7 microRNA, humanRibonucleoproteinsRNA, MessengerRNA, Small UntranslatedUracil

Identifiers

PMID19508234
PMCPMC2906378
OpenAlexW2125329241

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.