Evidence map›Paper›PMID 35018467›Full record

ArticleNucleic acids research2022

Ribosomal leaky scanning through a translated uORF requires eIF4G2.

Victoria V Smirnova, Ekaterina D Shestakova, Daria S Nogina, Polina A Mishchenko, Tatiana A Prikazchikova, Timofei S Zatsepin, Ivan V Kulakovskiy, Ivan N Shatsky, Ilya M Terenin

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.4field-weighted citation impact, top 10% 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

27 citing papers in PubMed, 37 citations in OpenAlex.

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  16. An epitope encoded by uORF ofMolecular therapy oncolytics · 2023
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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

9 authors at 3 institutions in 1 country.

Victoria V SmirnovaBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119234, Russia.ORCID 0000-0002-1472-3555
Ekaterina D ShestakovaFaculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow 119234, Russia.ORCID 0000-0002-1562-0179
Daria S NoginaFaculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow 119234, Russia.ORCID 0000-0002-0593-2726
Polina A MishchenkoFaculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow 119234, Russia.ORCID 0000-0002-7546-9204
Tatiana A PrikazchikovaSkolkovo Institute of Science and Technology, Skolkovo, Moscow 121205, Russia.
Timofei S ZatsepinSkolkovo Institute of Science and Technology, Skolkovo, Moscow 121205, Russia.ORCID 0000-0003-0030-9174
Ivan V KulakovskiyCenter for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia.ORCID 0000-0002-6554-8128
Ivan N ShatskyBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119234, Russia.ORCID 0000-0002-3384-0589
Ilya M TereninBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119234, Russia.ORCID 0000-0002-4459-0781
Lomonosov Moscow State University · RUSkolkovo Institute of Science and Technology · RUEngelhardt Institute of Molecular Biology · RU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

eIF4G2 (DAP5 or Nat1) is a homologue of the canonical translation initiation factor eIF4G1 in higher eukaryotes but its function remains poorly understood. Unlike eIF4G1, eIF4G2 does not interact with the cap-binding protein eIF4E and is believed to drive translation under stress when eIF4E activity is impaired. Here, we show that eIF4G2 operates under normal conditions as well and promotes scanning downstream of the eIF4G1-mediated 40S recruitment and cap-proximal scanning. Specifically, eIF4G2 facilitates leaky scanning for a subset of mRNAs. Apparently, eIF4G2 replaces eIF4G1 during scanning of 5' UTR and the necessity for eIF4G2 only arises when eIF4G1 dissociates from the scanning complex. In particular, this event can occur when the leaky scanning complexes interfere with initiating or elongating 80S ribosomes within a translated uORF. This mechanism is therefore crucial for higher eukaryotes which are known to have long 5' UTRs with highly frequent uORFs. We suggest that uORFs are not the only obstacle on the way of scanning complexes towards the main start codon, because certain eIF4G2 mRNA targets lack uORF(s). Thus, higher eukaryotes possess two distinct scanning complexes: the principal one that binds mRNA and initiates scanning, and the accessory one that rescues scanning when the former fails.

Indexed as

Eukaryotic Initiation Factor-4GHumansOpen Reading FramesProtein BiosynthesisRibosomesRNA, MessengerEIF4G2 protein, humanEukaryotic Initiation Factor-4GRNA, Messenger

Identifiers

PMID35018467
PMCPMC8789081
OpenAlexW4206063378

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.