Evidence map›Paper›PMID 39095657›Full record

ArticleNature cell biology2024

Systematic loss-of-function screens identify pathway-specific functional circular RNAs.

Ling Liu, Matthew Neve, Laura Perlaza-Jimenez, Xinqi Xi, Jacob Purcell, Azelle Hawdon, Simon J Conn, Jennifer Zenker, Pablo Tamayo, Gregory J Goodall and 1 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature cell biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Genome stability disrupted by the circRBM39(4,5,6)-RPA2 axis represses breast tumorigenesis.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  2. Article
  3. Review
  4. 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

11 authors.

Ling Liu *Department of Biochemistry and Molecular Biology, and Cancer Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.ORCID http://orcid.org/0009-0001-3822-1111
Matthew Neve *Department of Biochemistry and Molecular Biology, and Cancer Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
Laura Perlaza-JimenezDepartment of Biochemistry and Molecular Biology, and Cancer Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
Xinqi XiDepartment of Biochemistry and Molecular Biology, and Cancer Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
Jacob PurcellDepartment of Biochemistry and Molecular Biology, and Cancer Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
Azelle HawdonAustralian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia.ORCID http://orcid.org/0000-0002-8935-0597
Simon J ConnFlinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Bedford Park, South Australia, Australia.ORCID http://orcid.org/0000-0002-1376-4515
Jennifer ZenkerAustralian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia.ORCID http://orcid.org/0000-0002-9929-2909
Pablo TamayoDivision of Genomics and Precision Medicine, Department of Medicine, Moores Cancer Center, University of California San Diego, La Jolla, CA, USA.
Gregory J GoodallCentre for Cancer Biology, An alliance of University of South Australia and SA Pathology, Adelaide, South Australia, Australia.ORCID http://orcid.org/0000-0003-1294-0692
Joseph RosenbluhDepartment of Biochemistry and Molecular Biology, and Cancer Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia. sefi.rosenbluh@monash.edu.ORCID http://orcid.org/0000-0001-9815-8049

Funding

Department of Education and Training | Australian Research Council (ARC) DP210101755Department of Health | National Health and Medical Research Council (NHMRC) GNT1198014
6 · The paper itself

Abstract

Circular RNA (circRNA) is covalently closed, single-stranded RNA produced by back-splicing. A few circRNAs have been implicated as functional; however, we lack understanding of pathways that are regulated by circRNAs. Here we generated a pooled short-hairpin RNA library targeting the back-splice junction of 3,354 human circRNAs that are expressed at different levels (ranging from low to high) in humans. We used this library for loss-of-function proliferation screens in a panel of 18 cancer cell lines from four tissue types harbouring mutations leading to constitutive activity of defined pathways. Both context-specific and non-specific circRNAs were identified. Some circRNAs were found to directly regulate their precursor, whereas some have a function unrelated to their precursor. We validated these observations with a secondary screen and uncovered a role for circRERE(4-10) and circHUWE1(22,23), two cell-essential circRNAs, circSMAD2(2-6), a WNT pathway regulator, and circMTO1(2,RI,3), a regulator of MAPK signalling. Our work sheds light on pathways regulated by circRNAs and provides a catalogue of circRNAs with a measurable function.

Indexed as

Cell ProliferationRNA, CircularCell Line, TumorGene Expression Regulation, NeoplasticGene LibraryHumansRNARNA SplicingSignal TransductionWnt Signaling PathwayRNARNA, Circular

Identifiers

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.