Evidence map›Paper›PMID 33256807›Full record

ArticleGenome medicine2020

Pervasive generation of non-canonical subgenomic RNAs by SARS-CoV-2.

Jason Nomburg, Matthew Meyerson, James A DeCaprio

Open access · goldAbstract read
In one paragraph

Article in Genome medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
8.3field-weighted citation impact, top 1% 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

47 citing papers in PubMed, 69 citations in OpenAlex.

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  15. sgRNAs: A SARS-CoV-2 emerging issue.Aspects of molecular medicine · 2023
    Review
  16. Article
  17. Biology of the SARS-CoV-2 Coronavirus.Biochemistry. Biokhimiia · 2022
    Review
  18. Review
  19. Article
  20. Article
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.

Jason NomburgDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Matthew MeyersonDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. matthew_meyerson@dfci.harvard.edu.
James A DeCaprioDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. james_decaprio@dfci.harvard.edu.ORCID 0000-0002-0896-167X
Broad Institute · USBrigham and Women's Hospital · US

Funding

PROJECT 4: Interrogating PP2A Signaling in Human CancersP01CA203655 · NCI · DANA-FARBER CANCER INST · PI DECAPRIO, JAMES A. · 2017 to 2021
$8.0M
NCI NIH HHS P01 CA203655U.S. Public Health Service P01CA203655U.S. Public Health Service R35CA232128
6 · The paper itself

Abstract

backgroundSARS-CoV-2, a positive-sense RNA virus in the family Coronaviridae, has caused a worldwide pandemic of coronavirus disease 2019 or COVID-19. Coronaviruses generate a tiered series of subgenomic RNAs (sgRNAs) through a process involving homology between transcriptional regulatory sequences (TRS) located after the leader sequence in the 5' UTR (the TRS-L) and TRS located near the start of ORFs encoding structural and accessory proteins (TRS-B) near the 3' end of the genome. In addition to the canonical sgRNAs generated by SARS-CoV-2, non-canonical sgRNAs (nc-sgRNAs) have been reported. However, the consistency of these nc-sgRNAs across viral isolates and infection conditions is unknown. The comprehensive definition of SARS-CoV-2 RNA products is a key step in understanding SARS-CoV-2 pathogenesis.

methodsHere, we report an integrative analysis of eight independent SARS-CoV-2 transcriptomes generated using three sequencing strategies, five host systems, and seven viral isolates. Read-mapping to the SARS-CoV-2 genome was used to determine the 5' and 3' coordinates of all junctions in viral RNAs identified in these samples.

resultsUsing junctional abundances, we show nc-sgRNAs make up as much as 33% of total sgRNAs in cell culture models of infection, are largely consistent in abundance across independent transcriptomes, and increase in abundance over time during infection. By assessing the homology between sequences flanking the 5' and 3' junction points, we show that nc-sgRNAs are not associated with TRS-like homology. By incorporating read coverage information, we find strong evidence for subgenomic RNAs that contain only 5' regions of ORF1a. Finally, we show that non-canonical junctions change the landscape of viral open reading frames.

conclusionsWe identify canonical and non-canonical junctions in SARS-CoV-2 sgRNAs and show that these RNA products are consistently generated by many independent viral isolates and sequencing approaches. These analyses highlight the diverse transcriptional activity of SARS-CoV-2 and offer important insights into SARS-CoV-2 biology.

Indexed as

5' Untranslated RegionsOpen Reading FramesPandemicsCOVID-19HumansRNA, ViralSARS-CoV-25' Untranslated RegionsRNA, ViralCOVID-19Direct RNA sequencingSARS-CoV-2Transcription

Identifiers

PMID33256807
PMCPMC7704119
OpenAlexW3106919367

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.