Evidence map›Paper›PMID 31330067›Full record

ArticleThe EMBO journal2019

Let-7a-regulated translational readthrough of mammalian AGO1 generates a microRNA pathway inhibitor.

Anumeha Singh, Lekha E Manjunath, Pradipta Kundu, Sarthak Sahoo, Arpan Das, Harikumar R Suma, Paul L Fox, Sandeep M Eswarappa

Open access · hybridAbstract read
In one paragraph

Article in The EMBO journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
3.1field-weighted citation impact, top 7% 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

19 citing papers in PubMed, 54 citations in OpenAlex.

  1. Review
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  3. Response to Suresh et al.The EMBO journal · 2025
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  11. Distal nucleotides affect the rate of stop codon read-through.Quantitative biology (Beijing, China) · 2023
    Article
  12. Article
  13. Review
  14. Article
  15. Nonsense suppression therapies in human genetic diseases.Cellular and molecular life sciences : CMLS · 2021
    Review
  16. Stop codon read-through of mammalianThe Journal of biological chemistry · 2020
    Article
  17. Article
  18. Article
  19. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 2 countries.

Anumeha SinghDepartment of Biochemistry, Indian Institute of Science, Bengaluru, Karnataka, India.
Lekha E ManjunathDepartment of Biochemistry, Indian Institute of Science, Bengaluru, Karnataka, India.
Pradipta KunduDepartment of Microbiology and Cell Biology, Indian Institute of Science, Bengaluru, Karnataka, India.
Sarthak SahooDepartment of Biochemistry, Indian Institute of Science, Bengaluru, Karnataka, India.
Arpan DasDepartment of Biochemistry, Indian Institute of Science, Bengaluru, Karnataka, India.
Harikumar R SumaDepartment of Biochemistry, Indian Institute of Science, Bengaluru, Karnataka, India.
Paul L FoxDepartment of Cellular and Molecular Medicine, The Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Sandeep M EswarappaDepartment of Biochemistry, Indian Institute of Science, Bengaluru, Karnataka, India.ORCID 0000-0002-7903-5198
Indian Institute of Science Bangalore · INCleveland Clinic Lerner College of Medicine · US

Funding

CSIR-UGCDBT-Wellcome Trust India Alliance IA/I/15/1/501833DST-SERB, India YSS/2015/000989KVPY Fellowship, IndiaWellcome TrustWomen Scientist Scheme from DST, India SR/WOS-A/LS-1204/2015
6 · The paper itself

Abstract

Translational readthrough generates proteins with extended C-termini, which often possess distinct properties. Here, we have used various reporter assays to demonstrate translational readthrough of AGO1 mRNA. Analysis of ribosome profiling data and mass spectrometry data provided additional evidence for translational readthrough of AGO1. The endogenous readthrough product, Ago1x, could be detected by a specific antibody both in vitro and in vivo. This readthrough process is directed by a cis sequence downstream of the canonical AGO1 stop codon, which is sufficient to drive readthrough even in a heterologous context. This cis sequence has a let-7a miRNA-binding site, and readthrough is promoted by let-7a miRNA. Interestingly, Ago1x can load miRNAs on target mRNAs without causing post-transcriptional gene silencing, due to its inability to interact with GW182. Because of these properties, Ago1x can serve as a competitive inhibitor of miRNA pathway. In support of this, we observed increased global translation in cells overexpressing Ago1x. Overall, our results reveal a negative feedback loop in the miRNA pathway mediated by the translational readthrough product of AGO1.

Indexed as

Protein BiosynthesisArgonaute ProteinsAutoantigensBinding SitesCodon, TerminatorEukaryotic Initiation FactorsFeedback, PhysiologicalGene Expression RegulationHEK293 CellsHeLa CellsHumansMicroRNAsRibosomesRNA-Binding ProteinsSignal TransductionAGO1 protein, humanArgonaute ProteinsAutoantigensCodon, TerminatorEukaryotic Initiation FactorsMicroRNAsmirnlet7 microRNA, humanRNA-Binding ProteinsTNRC6A protein, humanArgonautelet-7amiRNAtranslational readthrough

Identifiers

PMID31330067
PMCPMC6694283
OpenAlexW2963525372

What OpenQuestion holds

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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.