Evidence map›Paper›PMID 35102684›Full record

ArticleAging cell2022

Loss of circRNAs from the crh-1 gene extends the mean lifespan in Caenorhabditis elegans.

David Knupp, Brian G Jorgensen, Hussam Z Alshareef, Jaffar M Bhat, Jeremy J Grubbs, Pedro Miura, Alexander M van der Linden

Open access · goldAbstract read
In one paragraph

Article in Aging cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.4field-weighted citation impact, top 20% 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

12 citing papers in PubMed, 19 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Loss of age-accumulatedFrontiers in aging neuroscience · 2025
    Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Review
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

7 authors at 1 institution in 1 country.

David KnuppDepartment of Biology, University of Nevada, Reno, Reno, Nevada, USA.
Brian G JorgensenDepartment of Biology, University of Nevada, Reno, Reno, Nevada, USA.
Hussam Z AlshareefDepartment of Biology, University of Nevada, Reno, Reno, Nevada, USA.ORCID 0000-0003-4980-3456
Jaffar M BhatDepartment of Biology, University of Nevada, Reno, Reno, Nevada, USA.
Jeremy J GrubbsDepartment of Biology, University of Nevada, Reno, Reno, Nevada, USA.
Pedro MiuraDepartment of Biology, University of Nevada, Reno, Reno, Nevada, USA.ORCID 0000-0002-8434-5027
Alexander M van der LindenDepartment of Biology, University of Nevada, Reno, Reno, Nevada, USA.ORCID 0000-0002-4870-7684
University of Nevada, Reno · US

Funding

Virtual Reality and Augmented Reality CoreP20GM103650 · NIGMS · UNIVERSITY OF NEVADA RENO · PI WEBSTER, MICHAEL A · 2012 to 2022
$20.9M
Role of age-accumulated circRNAs in long-term memoryR21AG058955 · NIA · UNIVERSITY OF NEVADA RENO · PI MIURA, PEDRO, VAN DER LINDEN, ALEXANDER MARTINUS · 2018 to 2020
$426k
NIA NIH HHS R21 AG058955NIGMS NIH HHS P20 GM103650
6 · The paper itself

Abstract

Accumulation of circular RNAs (circRNAs) during aging occurs on a genome-wide level for multiple organisms, but its significance is unknown. Generating circRNA loss-of-function mutants is difficult because the vast majority of these RNAs are comprised of exons shared with protein-coding mRNAs. In Caenorhabditis elegans, most circRNAs were previously found to accumulate during aging. Two of the most abundant, age-accumulating circRNAs are generated from exon 4 of the crh-1 gene (circ-crh-1). Here, we found that the biogenesis of circ-crh-1 was regulated by the double-stranded RNA-binding protein ADR-1. We identified Reverse Complementary Match (RCM) sequences in introns flanking circ-crh-1. Using CRISPR-Cas9, we deleted the downstream RCM and found that this completely eliminated expression of the circRNA without affecting linear mRNA expression from the crh-1 gene. Remarkably, worms lacking circ-crh-1 exhibited a significantly longer mean lifespan. Lifespan was partially restored to wild type by expression of circ-crh-1 in neural tissues. Widespread transcriptome alterations in circ-crh-1 mutants were identified using RNA-Seq. Moving forward, intronic RCM deletion using CRISPR should be a widely applicable method to identify lifespan-regulating circRNAs in C. elegans.

Indexed as

Adenosine DeaminaseCaenorhabditis elegans ProteinsRNA, CircularTranscription FactorsAnimalsCaenorhabditis elegansLongevityRNATranscriptomeAdenosine DeaminaseAdr-1 protein, C elegansCaenorhabditis elegans ProteinsCRH-1 protein, C elegansRNARNA, CircularTranscription FactorsagingCaenorhabditis eleganscircRNAcrh-1reverse complementary match

Identifiers

PMID35102684
PMCPMC8844124
OpenAlexW4210529544

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.