Evidence map›Paper›PMID 31665743›Full record

ArticleNucleic acids research2019

METTL15 introduces N4-methylcytidine into human mitochondrial 12S rRNA and is required for mitoribosome biogenesis.

Lindsey Van Haute, Alan G Hendrick, Aaron R D'Souza, Christopher A Powell, Pedro Rebelo-Guiomar, Michael E Harbour, Shujing Ding, Ian M Fearnley, Byron Andrews, Michal Minczuk

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
5.0field-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

63 citing papers in PubMed, 101 citations in OpenAlex.

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  15. METTL Family in Healthy and Disease.Molecular biomedicine · 2024
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3 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

10 authors at 2 institutions in 2 countries.

Lindsey Van HauteMedical Research Council Mitochondrial Biology Unit, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK.
Alan G HendrickSTORM Therapeutics Limited, Moneta Building, Babraham Research Campus, Cambridge CB22 3AT, UK.
Aaron R D'SouzaMedical Research Council Mitochondrial Biology Unit, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK.
Christopher A PowellMedical Research Council Mitochondrial Biology Unit, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK.
Pedro Rebelo-GuiomarMedical Research Council Mitochondrial Biology Unit, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK.
Michael E HarbourMedical Research Council Mitochondrial Biology Unit, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK.
Shujing DingMedical Research Council Mitochondrial Biology Unit, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK.
Ian M FearnleyMedical Research Council Mitochondrial Biology Unit, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK.
Byron AndrewsSTORM Therapeutics Limited, Moneta Building, Babraham Research Campus, Cambridge CB22 3AT, UK.
Michal MinczukMedical Research Council Mitochondrial Biology Unit, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK.
University of Cambridge · GBUniversidade do Porto · PT

Funding

Medical Research Council MC_UU_00015/4
6 · The paper itself

Abstract

Post-transcriptional RNA modifications, the epitranscriptome, play important roles in modulating the functions of RNA species. Modifications of rRNA are key for ribosome production and function. Identification and characterization of enzymes involved in epitranscriptome shaping is instrumental for the elucidation of the functional roles of specific RNA modifications. Ten modified sites have been thus far identified in the mammalian mitochondrial rRNA. Enzymes responsible for two of these modifications have not been characterized. Here, we identify METTL15, show that it is the main N4-methylcytidine (m4C) methyltransferase in human cells and demonstrate that it is responsible for the methylation of position C839 in mitochondrial 12S rRNA. We show that the lack of METTL15 results in a reduction of the mitochondrial de novo protein synthesis and decreased steady-state levels of protein components of the oxidative phosphorylation system. Without functional METTL15, the assembly of the mitochondrial ribosome is decreased, with the late assembly components being unable to be incorporated efficiently into the small subunit. We speculate that m4C839 is involved in the stabilization of 12S rRNA folding, therefore facilitating the assembly of the mitochondrial small ribosomal subunits. Taken together our data show that METTL15 is a novel protein necessary for efficient translation in human mitochondria.

Indexed as

CytidineHumansMethylationMethyltransferasesMitochondriaMitochondrial RibosomesOxidative PhosphorylationProtein BiosynthesisRNA FoldingRNA Processing, Post-TranscriptionalRNA, RibosomalCytidineMethyltransferasesMETTL16 protein, humanRNA, RibosomalRNA, ribosomal, 12S

Identifiers

PMID31665743
PMCPMC6821322
OpenAlexW2971757906

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.