Evidence map›Paper›PMID 26354771›Full record

ArticleRNA (New York, N.Y.)2015

Controlling mRNA stability and translation with the CRISPR endoribonuclease Csy4.

Erin K Borchardt, Leonidas A Vandoros, Michael Huang, Patrick E Lackey, William F Marzluff, Aravind Asokan

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 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
0.8field-weighted citation impact, top 28% 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

20 citing papers in PubMed, 38 citations in OpenAlex.

  1. Article
  2. Review
  3. Engineering and comparison of cas12a-based genome editing systems in plants.The Plant journal : for cell and molecular biology · 2025
    Article
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  9. RNAi-based Boolean gates in the yeastFrontiers in bioengineering and biotechnology · 2024
    Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. Article
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  19. Article
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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

6 authors at 1 institution in 1 country.

Erin K BorchardtCurriculum in Genetics and Molecular Biology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA Gene Therapy Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Leonidas A VandorosGene Therapy Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Michael HuangGene Therapy Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Patrick E LackeyDepartment of Biochemistry and Biophysics, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
William F MarzluffDepartment of Biochemistry and Biophysics, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Aravind AsokanGene Therapy Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA Department of Biochemistry and Biophysics, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA Department of Genetics, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
University of North Carolina at Chapel Hill · US

Funding

VECTOR AND MOLECULAR BIOLOGY COREP01HL112761 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SAMULSKI, RICHARD J · 2013 to 2017
$11.3M
CONTROL OF HISTONE MRNA SYNTHESISR01GM029832 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DOMINSKI, ZBIGNIEW, MARZLUFF, WILLIAM F. · 1985 to 2022
$9.0M
Determinants of AAV TropismR01HL089221 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Aravind Asokan · 2009 to 2026
$8.1M
NRSA IN GENETICST32GM007092 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SEKELSKY, JEFF J. · 1985 to 2019
$5.9M
Linking DNA Replication Origin Licensing with Cell Cycle ProgressionF31CA165891 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI COLEMAN, KATE E · 2013 to 2015
$85k
NHLBI NIH HHS P01 HL112761NHLBI NIH HHS P01HL112761NHLBI NIH HHS R01 HL089221NHLBI NIH HHS R01HL089221NIGMS NIH HHS 5T32 GM007092NIGMS NIH HHS R01 GM029832NIGMS NIH HHS T32 GM007092
6 · The paper itself

Abstract

The bacterial CRISPR endoribonuclease Csy4 has recently been described as a potential RNA processing tool. Csy4 recognizes substrate RNA through a specific 28-nt hairpin sequence and cleaves at the 3' end of the stem. To further explore applicability in mammalian cells, we introduced this hairpin at various locations in mRNAs derived from reporter transgenes and systematically evaluated the effects of Csy4-mediated processing on transgene expression. Placing the hairpin in the 5' UTR or immediately after the start codon resulted in efficient degradation of target mRNA by Csy4 and knockdown of transgene expression by 20- to 40-fold. When the hairpin was incorporated in the 3' UTR prior to the poly(A) signal, the mRNA was cleaved, but only a modest decrease in transgene expression (∼2.5-fold) was observed. In the absence of a poly(A) tail, Csy4 rescued the target mRNA substrate from degradation, resulting in protein expression, which suggests that the cleaved mRNA was successfully translated. In contrast, neither catalytically inactive (H29A) nor binding-deficient (R115A/R119A) Csy4 mutants were able to exert any of the effects described above. Generation of a similar 3' end by RNase P-mediated cleavage was unable to rescue transgene expression independent of Csy4. These results support the idea that the selective generation of the Csy4/hairpin complex resulting from cleavage of target mRNA might serve as a functional poly(A)/poly(A) binding protein (PABP) surrogate, stabilizing the mRNA and supporting translation. Although the exact mechanism(s) remain to be determined, our studies expand the potential utility of CRISPR nucleases as tools for controlling mRNA stability and translation.

Indexed as

3' Untranslated RegionsBacterial ProteinsCell LineCRISPR-Associated ProteinsEndoribonucleasesHEK293 CellsHumansInverted Repeat SequencesPoly AProtein BindingProtein BiosynthesisRNA, MessengerRNA Stability3' Untranslated RegionsBacterial ProteinsCRISPR-Associated ProteinsEndoribonucleasesPoly ARNA, MessengerCRISPRCsy4gene regulationmRNA stabilitytranslation

Identifiers

PMID26354771
PMCPMC4604432
OpenAlexW2116640224

What OpenQuestion holds

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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.