Evidence map›Paper›PMID 40501555›Full record

ArticlebioRxiv : the preprint server for biology2025

Genome-Wide Interrogation of SARS-CoV-2 RNA-Protein Interactions Uncovers Hidden Regulatory Sites.

Joy S Xiang, Karen X Zhao, Laliv Tadri, Kurt Tamaru, Brian A Yee, Katherine Rothamel, Jonathan C Schmok, Jasmine R Mueller, Samuel S Park, Assael A Madrigal and 11 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

21 authors.

Joy S XiangDivision of Biomedical Sciences, University of California, Riverside, Riverside, CA 92521, USA.ORCID 0000-0002-6400-1876
Karen X ZhaoDivision of Biomedical Sciences, University of California, Riverside, Riverside, CA 92521, USA.
Laliv TadriDivision of Biomedical Sciences, University of California, Riverside, Riverside, CA 92521, USA.
Kurt TamaruDivision of Biomedical Sciences, University of California, Riverside, Riverside, CA 92521, USA.
Brian A YeeDepartment of Cellular and Molecular Medicine, Institute for Genomic Medicine, UCSD Stem Cell Program, University of California, San Diego, La Jolla, CA 92037, USA.
Katherine RothamelDepartment of Cellular and Molecular Medicine, Institute for Genomic Medicine, UCSD Stem Cell Program, University of California, San Diego, La Jolla, CA 92037, USA.
Jonathan C SchmokDepartment of Cellular and Molecular Medicine, Institute for Genomic Medicine, UCSD Stem Cell Program, University of California, San Diego, La Jolla, CA 92037, USA.
Jasmine R MuellerDepartment of Cellular and Molecular Medicine, Institute for Genomic Medicine, UCSD Stem Cell Program, University of California, San Diego, La Jolla, CA 92037, USA.
Samuel S ParkDepartment of Cellular and Molecular Medicine, Institute for Genomic Medicine, UCSD Stem Cell Program, University of California, San Diego, La Jolla, CA 92037, USA.
Assael A MadrigalDepartment of Cellular and Molecular Medicine, Institute for Genomic Medicine, UCSD Stem Cell Program, University of California, San Diego, La Jolla, CA 92037, USA.
Rachael N McVicarSanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
Elizabeth M KwongSanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
Ben A CrokerDepartment of Pediatrics, University of California San Diego School of Medicine, La Jolla, CA 92037, USA.
Alex E ClarkDepartment of Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
Aaron F CarlinDepartment of Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
Charly AcevedoDivision of Biomedical Sciences, University of California, Riverside, Riverside, CA 92521, USA.
Declan McColeDivision of Biomedical Sciences, University of California, Riverside, Riverside, CA 92521, USA.
Seán E O'LearyDepartment of Biochemistry, University of California, Riverside, Riverside, CA 92521, USA.
Rong HaiDepartment of Microbiology and Plant Pathology, University of California, Riverside, Riverside, CA 92521, USA.
Sandra L LeibelDepartment of Pediatrics, University of California San Diego School of Medicine, La Jolla, CA 92037, USA.
Gene W YeoDepartment of Cellular and Molecular Medicine, Institute for Genomic Medicine, UCSD Stem Cell Program, University of California, San Diego, La Jolla, CA 92037, USA.

Funding

Deconvolution of pro- and anti-viral responses to Dengue virus and Zika Virus infectionsK08AI130381 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CARLIN, AARON F. · 2019 to 2023
$1.0M
Illumina NovaSeq 6000 Sequencing SystemS10OD026929 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JEPSEN, KRISTEN LYNN · 2019 to 2019
$600k
NIAID NIH HHS K08 AI130381NIH HHS S10 OD026929
6 · The paper itself

Abstract

The global impact of the COVID-19 pandemic underscores the critical need for a comprehensive understanding of SARS-CoV-2 replication mechanisms. While the central roles of the RNA dependent RNA polymerase (NSP12), primase protein (NSP8), and nucleocapsid protein (N) in the virus life cycle are extensively studied, the precise nature of their interactions with the full-length viral RNA genome remain incompletely characterized. In this study, we sought to address this knowledge gap by employing enhanced crosslinking and immunoprecipitation (eCLIP) to map the binding sites of NSP8, NSP12, and N proteins across the SARS-CoV-2 genome at early stages of viral RNA and protein synthesis and late stages of virion assembly. Our findings revealed interactions of NSP8 and NSP12 to the 5' and 3' untranslated regions (UTRs) of both positive and negative sense RNA, regions known to regulate viral replication, transcription, and translation. We identified a surprising and essential NSP12 binding site within the RNA sequence encoding the conserved Y1 domain of NSP3, which regulates RNA abundance upstream of the site. Additionally, we found that N protein interacts with the 5' UTR and influences translation efficiency. Finally, we report a novel regulatory function of N protein in modulating ribosomal frameshifting proximal to the frameshift element, a crucial process for maintaining viral protein stoichiometry. Our results provide a detailed molecular map of SARS-CoV-2 protein-RNA interactions, revealing potential therapeutic targets for attenuating viral fitness and informing the development of next-generation antiviral strategies.

Identifiers

PMID40501555
PMCPMC12154810

What OpenQuestion holds

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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.