Evidence map›Paper›PMID 35849342›Full record

ArticleNucleic acids research2022

Cap-independent translation and a precisely located RNA sequence enable SARS-CoV-2 to control host translation and escape anti-viral response.

Boris Slobodin, Urmila Sehrawat, Anastasia Lev, Daniel Hayat, Binyamin Zuckerman, Davide Fraticelli, Ariel Ogran, Amir Ben-Shmuel, Elad Bar-David, Haim Levy and 2 more

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 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
6.7field-weighted citation impact, top 2% 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

32 citing papers in PubMed, 45 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

12 authors at 4 institutions in 2 countries.

Boris SlobodinDepartment of Biomolecular Sciences, The Weizmann Institute of Science, Rehovot 76100, Israel.ORCID 0000-0002-6324-2715
Urmila SehrawatDepartment of Biomolecular Sciences, The Weizmann Institute of Science, Rehovot 76100, Israel.
Anastasia LevDepartment of Biomolecular Sciences, The Weizmann Institute of Science, Rehovot 76100, Israel.
Daniel HayatDepartment of Biomolecular Sciences, The Weizmann Institute of Science, Rehovot 76100, Israel.
Binyamin ZuckermanDepartment of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel.ORCID 0000-0002-6216-011X
Davide FraticelliDepartment of Biomolecular Sciences, The Weizmann Institute of Science, Rehovot 76100, Israel.
Ariel OgranDepartment of Biomolecular Sciences, The Weizmann Institute of Science, Rehovot 76100, Israel.
Amir Ben-ShmuelDepartment of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona 7410001 Israel.
Elad Bar-DavidDepartment of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona 7410001 Israel.
Haim LevyDepartment of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona 7410001 Israel.
Igor UlitskyDepartment of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel.ORCID 0000-0003-0555-6561
Rivka DiksteinDepartment of Biomolecular Sciences, The Weizmann Institute of Science, Rehovot 76100, Israel.ORCID 0000-0002-6251-4723
Weizmann Institute of Science · ILIsrael Institute for Biological Research · ILGladstone Institutes · USMemorial Sloan Kettering Cancer Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Translation of SARS-CoV-2-encoded mRNAs by the host ribosomes is essential for its propagation. Following infection, the early expressed viral protein NSP1 binds the ribosome, represses translation, and induces mRNA degradation, while the host elicits an anti-viral response. The mechanisms enabling viral mRNAs to escape this multifaceted repression remain obscure. Here we show that expression of NSP1 leads to destabilization of multi-exon cellular mRNAs, while intron-less transcripts, such as viral mRNAs and anti-viral interferon genes, remain relatively stable. We identified a conserved and precisely located cap-proximal RNA element devoid of guanosines that confers resistance to NSP1-mediated translation inhibition. Importantly, the primary sequence rather than the secondary structure is critical for protection. We further show that the genomic 5'UTR of SARS-CoV-2 drives cap-independent translation and promotes expression of NSP1 in an eIF4E-independent and Torin1-resistant manner. Upon expression, NSP1 further enhances cap-independent translation. However, the sub-genomic 5'UTRs are highly sensitive to eIF4E availability, rendering viral propagation partially sensitive to Torin1. We conclude that the combined NSP1-mediated degradation of spliced mRNAs and translation inhibition of single-exon genes, along with the unique features present in the viral 5'UTRs, ensure robust expression of viral mRNAs. These features can be exploited as potential therapeutic targets.

Indexed as

SARS-CoV-2Viral Nonstructural Proteins5' Untranslated RegionsBase SequenceCOVID-19Eukaryotic Initiation Factor-4EHumansProtein BiosynthesisRNA CapsRNA, MessengerRNA, Viral5' Untranslated RegionsEukaryotic Initiation Factor-4EORF1ab polyprotein, SARS-CoV-2RNA CapsRNA, MessengerRNA, ViralViral Nonstructural Proteins

Identifiers

PMID35849342
PMCPMC9371909
OpenAlexW4285800750

What OpenQuestion holds

Textmetadata
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.