Evidence map›Paper›PMID 37144468›Full record

ArticleNucleic acids research2023

Translational fidelity screens in mammalian cells reveal eIF3 and eIF4G2 as regulators of start codon selectivity.

Richard She, Jingchuan Luo, Jonathan S Weissman

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
4.2field-weighted citation impact, top 6% 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

20 citing papers in PubMed, 27 citations in OpenAlex.

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  16. CRISPRi screens identify the lncRNA,Proceedings of the National Academy of Sciences of the United States of America · 2024
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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

3 authors at 2 institutions in 1 country.

Richard SheWhitehead Institute for Biomedical Research, Cambridge, MA, USA.ORCID 0000-0003-3056-3800
Jingchuan LuoWhitehead Institute for Biomedical Research, Cambridge, MA, USA.ORCID 0000-0002-6450-7172
Jonathan S WeissmanWhitehead Institute for Biomedical Research, Cambridge, MA, USA.
Whitehead Institute for Biomedical Research · USHoward Hughes Medical Institute · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The translation initiation machinery and the ribosome orchestrate a highly dynamic scanning process to distinguish proper start codons from surrounding nucleotide sequences. Here, we performed genome-wide CRISPRi screens in human K562 cells to systematically identify modulators of the frequency of translation initiation at near-cognate start codons. We observed that depletion of any eIF3 core subunit promoted near-cognate start codon usage, though sensitivity thresholds of each subunit to sgRNA-mediated depletion varied considerably. Double sgRNA depletion experiments suggested that enhanced near-cognate usage in eIF3D depleted cells required canonical eIF4E cap-binding and was not driven by eIF2A or eIF2D-dependent leucine tRNA initiation. We further characterized the effects of eIF3D depletion and found that the N-terminus of eIF3D was strictly required for accurate start codon selection, whereas disruption of the cap-binding properties of eIF3D had no effect. Lastly, depletion of eIF3D activated TNFα signaling via NF-κB and the interferon gamma response. Similar transcriptional profiles were observed upon knockdown of eIF1A and eIF4G2, which also promoted near-cognate start codon usage, suggesting that enhanced near-cognate usage could potentially contribute to NF-κB activation. Our study thus provides new avenues to study the mechanisms and consequences of alternative start codon usage.

Indexed as

Eukaryotic Initiation Factor-3RNA, Guide, CRISPR-Cas SystemsCodon, InitiatorEukaryotic Initiation Factor-4EEukaryotic Initiation Factor-4GHumansNF-kappa BPeptide Chain Initiation, TranslationalProtein BiosynthesisRibosomesCodon, InitiatorEIF3D protein, humanEIF4E protein, humanEIF4G2 protein, humanEukaryotic Initiation Factor-3Eukaryotic Initiation Factor-4EEukaryotic Initiation Factor-4GNF-kappa BRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID37144468
PMCPMC10325891
OpenAlexW4372336318

What OpenQuestion holds

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LicenceCC BY
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.