Evidence map›Paper›PMID 36095031›Full record

ArticlePLoS pathogens2022

Novel viral splicing events and open reading frames revealed by long-read direct RNA sequencing of adenovirus transcripts.

Alexander M Price, Robert T Steinbock, Richard Lauman, Matthew Charman, Katharina E Hayer, Namrata Kumar, Edwin Halko, Krystal K Lum, Monica Wei, Angus C Wilson and 3 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
4.3field-weighted citation impact, top 5% 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

28 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
  2. Article
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  5. Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Mysteries of adenovirus packaging.Journal of virology · 2025
    Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Nanopore Guided Annotation of Transcriptome Architectures.bioRxiv : the preprint server for biology · 2024
    Article
  17. The adenovirus DNA-binding protein DBP.Journal of virology · 2024
    Review
  18. Article
  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

13 authors at 4 institutions in 2 countries.

Alexander M PriceDivision of Protective Immunity, Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
Robert T SteinbockCell & Molecular Biology Graduate Group, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Richard LaumanDivision of Protective Immunity, Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
Matthew CharmanDivision of Protective Immunity, Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
Katharina E HayerDepartment of Biomedical and Health Informatics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
Namrata KumarDivision of Protective Immunity, Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
Edwin HalkoDivision of Protective Immunity, Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
Krystal K LumDivision of Protective Immunity, Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
Monica WeiCell & Molecular Biology Graduate Group, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Angus C WilsonDepartment of Microbiology, New York University School of Medicine, New York city, New York, United States of America.
Benjamin A GarciaDepartment of Biochemistry and Biophysics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.
Daniel P DepledgeDepartment of Microbiology, New York University School of Medicine, New York city, New York, United States of America.
Matthew D WeitzmanDivision of Protective Immunity, Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.ORCID 0000-0001-9713-167X
Children's Hospital of Philadelphia · USUniversity of Pennsylvania · USMedizinische Hochschule Hannover · DENew York University · US

Funding

Shared Resources Core 2: Quantitative Proteomics CoreP01CA196539 · NCI · ROCKEFELLER UNIVERSITY · PI MUIR, TOM · 2015 to 2024
$17.6M
Viral modulation of epitranscriptomic mechanismsR01AI118891 · NIAID · WASHINGTON UNIVERSITY · PI GARCIA, BENJAMIN A, WEITZMAN, MATTHEW D. · 2015 to 2025
$5.4M
Training In Tumor VirologyT32CA115299 · NCI · UNIVERSITY OF PENNSYLVANIA · PI ROBERTSON, ERLE S. · 2006 to 2021
$4.7M
Double-stranded RNA during DNA virus infectionR01AI145266 · NIAID · CHILDREN'S HOSP OF PHILADELPHIA · PI WEITZMAN, MATTHEW D. · 2019 to 2023
$3.0M
EPITRANSCRIPTOMIC REGULATION OF CYTOMEGALOVIRUS INFECTIONR01AI152543 · NIAID · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI DEPLEDGE, DANIEL PEARCE, MOHR, IAN J · 2020 to 2025
$2.7M
Adenovirus manipulation of cellular chromatin to overcome host responsesR01AI121321 · NIAID · CHILDREN'S HOSP OF PHILADELPHIA · PI WEITZMAN, MATTHEW D. · 2018 to 2022
$2.7M
Quantitative mass spectrometry for comprehending epigenetic mechanisms in a new underlying neurological developmental disorderR01HD106051 · NICHD · WASHINGTON UNIVERSITY · PI Benjamin A Garcia · 2022 to 2026
$2.6M
Non-canonical chimeric proteins generated during Adenovirus infectionR21AI154654 · NIAID · CHILDREN'S HOSP OF PHILADELPHIA · PI WEITZMAN, MATTHEW D. · 2021 to 2022
$484k
Viral manipulation of neuronal microRNAs to maintain trophic support and HSV latencyR21AI147163 · NIAID · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI WILSON, ANGUS C · 2019 to 2020
$475k
Modeling herpes simplex virus latency in human neuronsR21AI130618 · NIAID · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI WILSON, ANGUS C · 2018 to 2019
$466k
dsRNA production and sensing during DNA virus infectionK99AI159049 · NIAID · CHILDREN'S HOSP OF PHILADELPHIA · PI PRICE, ALEXANDER MATTHEW · 2021 to 2022
$254k
Investigating the role of m6A RNA methylation during adenovirus infectionF32AI138432 · NIAID · CHILDREN'S HOSP OF PHILADELPHIA · PI PRICE, ALEXANDER MATTHEW · 2018 to 2020
$126k
NCI NIH HHS P01 CA196539NCI NIH HHS T32 CA115299NIAID NIH HHS F32 AI138432NIAID NIH HHS K99 AI159049NIAID NIH HHS R01 AI118891NIAID NIH HHS R01 AI121321NIAID NIH HHS R01 AI145266NIAID NIH HHS R01 AI152543NIAID NIH HHS R21 AI130618NIAID NIH HHS R21 AI147163NIAID NIH HHS R21 AI154654NICHD NIH HHS R01 HD106051
6 · The paper itself

Abstract

Adenovirus is a common human pathogen that relies on host cell processes for transcription and processing of viral RNA and protein production. Although adenoviral promoters, splice junctions, and polyadenylation sites have been characterized using low-throughput biochemical techniques or short read cDNA-based sequencing, these technologies do not fully capture the complexity of the adenoviral transcriptome. By combining Illumina short-read and nanopore long-read direct RNA sequencing approaches, we mapped transcription start sites and RNA cleavage and polyadenylation sites across the adenovirus genome. In addition to confirming the known canonical viral early and late RNA cassettes, our analysis of splice junctions within long RNA reads revealed an additional 35 novel viral transcripts that meet stringent criteria for expression. These RNAs include fourteen new splice junctions which lead to expression of canonical open reading frames (ORFs), six novel ORF-containing transcripts, and 15 transcripts encoding for messages that could alter protein functions through truncation or fusion of canonical ORFs. In addition, we detect RNAs that bypass canonical cleavage sites and generate potential chimeric proteins by linking distinct gene transcription units. Among these chimeric proteins we detected an evolutionarily conserved protein containing the N-terminus of E4orf6 fused to the downstream DBP/E2A ORF. Loss of this novel protein, E4orf6/DBP, was associated with aberrant viral replication center morphology and poor viral spread. Our work highlights how long-read sequencing technologies combined with mass spectrometry can reveal further complexity within viral transcriptomes and resulting proteomes.

Indexed as

AdenoviridaeRNA, ViralDNA, ComplementaryHumansOpen Reading FramesProteomeRecombinant Fusion ProteinsRNA SplicingSequence Analysis, RNATranscriptomeDNA, ComplementaryProteomeRecombinant Fusion ProteinsRNA, Viral

Identifiers

PMID36095031
PMCPMC9499273
OpenAlexW4295605370

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.