Evidence map›Paper›PMID 29889857›Full record

ArticlePLoS biology2018

DENR-MCTS1 heterodimerization and tRNA recruitment are required for translation reinitiation.

Yasar Luqman Ahmed, Sibylle Schleich, Jonathan Bohlen, Nicolas Mandel, Bernd Simon, Irmgard Sinning, Aurelio A Teleman

Open access · goldAbstract read
In one paragraph

Article in PLoS biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

33 citing papers in PubMed, 44 citations in OpenAlex.

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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

7 authors at 3 institutions in 1 country.

Yasar Luqman AhmedHeidelberg University Biochemistry Center (BZH), Heidelberg, Germany.
Sibylle SchleichGerman Cancer Research Center (DKFZ), Heidelberg, Germany.
Jonathan BohlenGerman Cancer Research Center (DKFZ), Heidelberg, Germany.
Nicolas MandelGerman Cancer Research Center (DKFZ), Heidelberg, Germany.
Bernd SimonEuropean Molecular Biology Laboratory (EMBL), Structural and Computational Biology Unit, Heidelberg, Germany.
Irmgard SinningHeidelberg University Biochemistry Center (BZH), Heidelberg, Germany.
Aurelio A TelemanGerman Cancer Research Center (DKFZ), Heidelberg, Germany.ORCID 0000-0002-4237-9368
German Cancer Research Center · DEHeidelberg University · DEEuropean Molecular Biology Laboratory · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The succession of molecular events leading to eukaryotic translation reinitiation-whereby ribosomes terminate translation of a short open reading frame (ORF), resume scanning, and then translate a second ORF on the same mRNA-is not well understood. Density-regulated reinitiation and release factor (DENR) and multiple copies in T-cell lymphoma-1 (MCTS1) are implicated in promoting translation reinitiation both in vitro in translation extracts and in vivo. We present here the crystal structure of MCTS1 bound to a fragment of DENR. Based on this structure, we identify and experimentally validate that DENR residues Glu42, Tyr43, and Tyr46 are important for MCTS1 binding and that MCTS1 residue Phe104 is important for tRNA binding. Mutation of these residues reveals that DENR-MCTS1 dimerization and tRNA binding are both necessary for DENR and MCTS1 to promote translation reinitiation in human cells. These findings thereby link individual residues of DENR and MCTS1 to specific molecular functions of the complex. Since DENR-MCTS1 can bind tRNA in the absence of the ribosome, this suggests the DENR-MCTS1 complex could recruit tRNA to the ribosome during reinitiation analogously to the eukaryotic initiation factor 2 (eIF2) complex in cap-dependent translation.

Indexed as

Amino Acid SubstitutionCell Cycle ProteinsCrystallography, X-RayEukaryotic Initiation Factor-2Eukaryotic Initiation FactorsHeLa CellsHumansModels, MolecularMutagenesis, Site-DirectedOncogene ProteinsOpen Reading FramesPeptide Chain Initiation, TranslationalProtein Interaction Domains and MotifsProtein MultimerizationRibosomesRNA, TransferCell Cycle ProteinsDENR protein, humanEukaryotic Initiation Factor-2Eukaryotic Initiation FactorsMCTS1 protein, humanOncogene ProteinsRNA, Transfer

Identifiers

PMID29889857
PMCPMC6013234
OpenAlexW2804213753

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.