Evidence map›Paper›PMID 32955563›Full record

ArticleNucleic acids research2020

Comprehensive analysis of translation from overexpressed circular RNAs reveals pervasive translation from linear transcripts.

Hung Ho-Xuan, Petar Glažar, Claudia Latini, Kevin Heizler, Jacob Haase, Robert Hett, Marvin Anders, Franziska Weichmann, Astrid Bruckmann, Debbie Van den Berg and 4 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed
4.8field-weighted citation impact, top 4% 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

69 citing papers in PubMed, 91 citations in OpenAlex.

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  10. Evaluating the reliability of tools for mRNA annotation and IRES studies.bioRxiv : the preprint server for biology · 2026
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  18. The therapeutic potential of circular RNAs.Nature reviews. Genetics · 2025
    Review
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  20. Article

9 more citing papers are in PubMed but not listed here.

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

14 authors at 5 institutions in 2 countries.

Hung Ho-XuanRegensburg Center for Biochemistry (RCB), Laboratory for RNA Biology, University of Regensburg, Regensburg, Germany.
Petar GlažarLaboratory for Systems Biology of Gene Regulatory Elements, Berlin Institute for Medical Systems Biology, Max-Delbrück Center for Molecular Medicine, Berlin, Germany.
Claudia LatiniRegensburg Center for Biochemistry (RCB), Laboratory for RNA Biology, University of Regensburg, Regensburg, Germany.
Kevin HeizlerRegensburg Center for Biochemistry (RCB), Laboratory for RNA Biology, University of Regensburg, Regensburg, Germany.
Jacob HaaseInstitute of Molecular Medicine, Section for Molecular Cell Biology, Martin-Luther-University Halle-Wittenberg, Charles Tanford Protein Center, 06120 Halle, Germany.
Robert HettRegensburg Center for Biochemistry (RCB), Laboratory for RNA Biology, University of Regensburg, Regensburg, Germany.
Marvin AndersDepartment of Surgery, University Hospital Regensburg, Regensburg, Germany.
Franziska WeichmannRegensburg Center for Biochemistry (RCB), Laboratory for RNA Biology, University of Regensburg, Regensburg, Germany.
Astrid BruckmannRegensburg Center for Biochemistry (RCB), Laboratory for RNA Biology, University of Regensburg, Regensburg, Germany.
Debbie Van den BergDepartment of Cell Biology, Erasmus MC, Wytemaweg 80, 3015 CN, Rotterdam, Netherlands.
Stefan HüttelmaierInstitute of Molecular Medicine, Section for Molecular Cell Biology, Martin-Luther-University Halle-Wittenberg, Charles Tanford Protein Center, 06120 Halle, Germany.
Nikolaus RajewskyLaboratory for Systems Biology of Gene Regulatory Elements, Berlin Institute for Medical Systems Biology, Max-Delbrück Center for Molecular Medicine, Berlin, Germany.
Christina HacklDepartment of Surgery, University Hospital Regensburg, Regensburg, Germany.
Gunter MeisterRegensburg Center for Biochemistry (RCB), Laboratory for RNA Biology, University of Regensburg, Regensburg, Germany.
University of Regensburg · DEMartin Luther University Halle-Wittenberg · DEMax Delbrück Center · DEUniversity Hospital Regensburg · DEErasmus MC · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Circular RNAs (circRNAs) encompass a widespread and conserved class of RNAs, which are generated by back-splicing of downstream 5' to upstream 3' splice sites. CircRNAs are tissue-specific and have been implicated in diseases including cancer. They can function as sponges for microRNAs (miRNAs) or RNA binding proteins (RBPs), for example. Moreover, some contain open reading frames (ORFs) and might be translated. The functional relevance of such peptides, however, remains largely elusive. Here, we report that the ORF of circZNF609 is efficiently translated when expressed from a circZNF609 overexpression construct. However, endogenous proteins could not be detected. Moreover, initiation of circZNF609 translation is independent of m6A-generating enzyme METTL3 or RNA sequence elements such as internal ribosome entry sites (IRESs). Surprisingly, a comprehensive mutational analysis revealed that deletion constructs, which are deficient in producing circZNF609, still generate the observed protein products. This suggests that the apparent circZNF609 translation originates from trans-splicing by-products of the overexpression plasmids and underline that circRNA overexpression constructs need to be evaluated carefully, particularly when functional studies are performed.

Indexed as

Protein BiosynthesisBase SequenceGene Expression RegulationHEK293 CellsHumansInternal Ribosome Entry SitesMethyltransferasesMicroRNAsRNA-Binding ProteinsRNA, CircularRNA Splice SitesInternal Ribosome Entry SitesMethyltransferasesMETTL3 protein, humanMicroRNAsRNA-Binding ProteinsRNA, CircularRNA Splice Sites

Identifiers

PMID32955563
PMCPMC7544230
OpenAlexW3087442100

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.