Evidence map›Paper›PMID 39149912›Full record

ArticleNucleic acids research2024

KREH2 helicase represses ND7 mRNA editing in procyclic-stage Trypanosoma brucei by opposite modulation of canonical and 'moonlighting' gRNA utilization creating a proposed mRNA structure.

Joshua Meehan, Alasdair Ivens, Scott Grote, Tyler Rodshagen, Zihao Chen, Cody Goode, Sunil K Sharma, Vikas Kumar, Addison Frese, Zachary Goodall and 8 more

Abstract read
In one paragraph

Article in Nucleic acids research, 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. Article
  2. Article
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  4. 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

18 authors.

Joshua MeehanDepartment of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843, USA.ORCID 0000-0003-1617-2926
Alasdair IvensInstitute of Immunology and Infection Research, University of Edinburgh, Edinburgh, EH9 3FL, UK.
Scott GroteDepartment of Microbiology, Harvard Medical School, Boston, MA 02115, USA.
Tyler RodshagenCenter for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA 98109, USA.
Zihao ChenInstitute of Immunology and Infection Research, University of Edinburgh, Edinburgh, EH9 3FL, UK.
Cody GoodeDepartment of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843, USA.
Sunil K SharmaDepartment of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843, USA.
Vikas KumarDepartment of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843, USA.
Addison FreseDepartment of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843, USA.
Zachary GoodallDepartment of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843, USA.
Laura McCleskeyDepartment of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843, USA.
Rebecca SechristDepartment of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843, USA.
Lanying ZengDepartment of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843, USA.
Nicholas J SavillInstitute of Immunology and Infection Research, University of Edinburgh, Edinburgh, EH9 3FL, UK.
Silvi RouskinDepartment of Microbiology, Harvard Medical School, Boston, MA 02115, USA.
Achim SchnauferInstitute of Immunology and Infection Research, University of Edinburgh, Edinburgh, EH9 3FL, UK.ORCID 0000-0003-2132-5560
Suzanne M McDermottCenter for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA 98109, USA.
Jorge Cruz-ReyesDepartment of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843, USA.ORCID 0000-0003-0545-1508

Funding

IMSD at Texas A&M University: Initiative for Maximizing Student Diversity in Biomedical SciencesT32GM135748 · NIGMS · TEXAS A&M UNIVERSITY · PI BRINKMEYER-LANGFORD, CANDICE L., CHIU, WEIHSUEH A · 2020 to 2024
$1.2M
National Science Foundation 1616845NIGMS NIH HHS T32 GM135748Texas A&M X 248543
6 · The paper itself

Abstract

Unknown factors regulate mitochondrial U-insertion/deletion (U-indel) RNA editing in procyclic-form (PCF) and bloodstream-form (BSF) T. brucei. This editing, directed by anti-sense gRNAs, creates canonical protein-encoding mRNAs and may developmentally control respiration. Canonical editing by gRNAs that specify protein-encoding mRNA sequences occurs amid massive non-canonical editing of unclear sources and biological significance. We found PCF-specific repression at a major early checkpoint in mRNA ND7, involving helicase KREH2-dependent opposite modulation of canonical and non-canonical 'terminator' gRNA utilization. Terminator-programmed editing derails canonical editing and installs proposed repressive structure in 30% of the ND7 transcriptome. BSF-to-PCF differentiation in vitro recreated this negative control. Remarkably, KREH2-RNAi knockdown relieved repression and increased editing progression by reverting canonical/terminator gRNA utilization. ND7 transcripts lacking early terminator-directed editing in PCF exhibited similar negative editing control along the mRNA sequence, suggesting global modulation of gRNA utilization fidelity. The terminator is a 'moonlighting' gRNA also associated with mRNA COX3 canonical editing, so the gRNA transcriptome seems multifunctional. Thus, KREH2 is the first identified repressor in developmental editing control. This and our prior work support a model whereby KREH2 activates or represses editing in a stage and substrate-specific manner. KREH2's novel dual role tunes mitochondrial gene expression in either direction during development.

Indexed as

Protozoan ProteinsRNA EditingRNA, MessengerTrypanosoma brucei bruceiMitochondriaNADH DehydrogenaseRNA, Guide, CRISPR-Cas SystemsRNA, Guide, KinetoplastidaNADH DehydrogenaseProtozoan ProteinsRNA, Guide, CRISPR-Cas SystemsRNA, Guide, KinetoplastidaRNA, Messenger

Identifiers

PMID39149912
PMCPMC11514453

What Socratic 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 Socratic graph.