Evidence map›Paper›PMID 25449546›Full record

ArticleRNA (New York, N.Y.)2015

Efficient backsplicing produces translatable circular mRNAs.

Yang Wang, Zefeng Wang

Open access · bronzeAbstract read
In one paragraph

Article in RNA (New York, N.Y.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 416 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
416citing papers in PubMed, 2 pooled it
14.2field-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

416 citing papers in PubMed, 2 syntheses or guidelines pooled it, 666 citations in OpenAlex.

  1. Pooled it
  2. Alternative splicing and cancer: a systematic review.Signal transduction and targeted therapy · 2021
    Pooled it
  3. Review
  4. Review
  5. Article
  6. Article
  7. Review
  8. Acta pharmaceutica Sinica. B · 2026
    Review
  9. Review
  10. Role of non-coding RNAs in OOncology letters · 2026
    Review
  11. Review
  12. Article
  13. Review
  14. Review
  15. Article
  16. Circular RNAs: from transcriptional noise to engineered therapeutics.Frontiers in epigenetics and epigenomics · 2026
    Review
  17. Article
  18. Review
  19. Review
  20. Article

356 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

2 authors at 1 institution in 2 countries.

Yang WangInstitute of Cancer Stem Cell, the Second Affiliated Hospital, Cancer Center, Dalian Medical University, Dalian 116044, China Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Zefeng WangDepartment of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA zefeng@med.unc.edu.
University of North Carolina at Chapel Hill · US

Funding

Modulation of VEGF-A alternative splicing as new anti-angiogenic therapeuticsR01CA158283 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI WANG, ZEFENG · 2011 to 2015
$1.4M
Artificial site-specific RNA endonuclease as new Myotonic Dystrophy therapeuticsR21AR061640 · NIAMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI WANG, ZEFENG · 2011 to 2012
$358k
NCI NIH HHS R01 CA158283NCI NIH HHS R01-CA158283NIAMS NIH HHS R21 AR061640
6 · The paper itself

Abstract

While the human transcriptome contains a large number of circular RNAs (circRNAs), the functions of most circRNAs remain unclear. Sequence annotation suggests that most circRNAs are generated from splicing in reversed orders across exons. However, the mechanisms of this backsplicing are largely unknown. Here we constructed a single exon minigene containing split GFP, and found that the pre-mRNA indeed produces circRNA through efficient backsplicing in human and Drosophila cells. The backsplicing is enhanced by complementary introns that form double-stranded RNA structure to bring splice sites in proximity, but such structure is not required. Moreover, backsplicing is regulated by general splicing factors and cis-elements, but with regulatory rules distinct from canonical splicing. The resulting circRNA can be translated to generate functional proteins. Unlike linear mRNA, poly-adenosine or poly-thymidine in 3' UTR can inhibit circular mRNA translation. This study revealed that backsplicing can occur efficiently in diverse eukaryotes to generate circular mRNAs.

Indexed as

Alternative SplicingAnimalsDrosophila melanogasterGreen Fluorescent ProteinsHEK293 CellsHumansNucleic Acid ConformationProtein BiosynthesisRNA, MessengerGreen Fluorescent ProteinsRNA, Messengeralternative splicingbacksplicingcircular RNAsplicing factorstranslation

Identifiers

PMID25449546
PMCPMC4338345
OpenAlexW2128549339

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.