Evidence map›Paper›PMID 33330931›Full record

ArticleNucleic acids research2021

Sequence- and structure-specific cytosine-5 mRNA methylation by NSUN6.

Tommaso Selmi, Shobbir Hussain, Sabine Dietmann, Matthias Heiß, Kayla Borland, Sophia Flad, Jean-Michel Carter, Rebecca Dennison, Ya-Lin Huang, Stefanie Kellner and 2 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 136 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
136citing papers in PubMed, 1 pooled it
8.8field-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

136 citing papers in PubMed, 1 synthesis or guideline pooled it, 207 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Review
  5. Article
  6. Coordinated DNA 5-mC and RNA mExperimental & molecular medicine · 2026
    Article
  7. Review
  8. Article
  9. 5-Methylcytosine Analysis of miRNAs in Minimal Change Disease.Biotechnology and applied biochemistry · 2026
    Article
  10. Article
  11. Article
  12. Review
  13. mAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  14. Review
  15. mBiology direct · 2026
    Review
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article

76 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

12 authors at 6 institutions in 3 countries.

Tommaso SelmiDepartment of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK.
Shobbir HussainDepartment of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, UK.
Sabine DietmannWashington University School of Medicine in St. Louis, 660 S. Euclid Ave, St. Louis, MO 63110, USA.
Matthias HeißDepartment of Chemistry, Ludwig-Maximilians-University Munich, Butenandtstr. 5-13, Haus F, 81377 Munich, Germany.
Kayla BorlandDepartment of Chemistry, Ludwig-Maximilians-University Munich, Butenandtstr. 5-13, Haus F, 81377 Munich, Germany.
Sophia FladGerman Cancer Research Center - Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Jean-Michel CarterDepartment of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, UK.
Rebecca DennisonCambridge Institute of Public Health, University of Cambridge, Forvie Site, Robinson Way, Cambridge CB2 0SR, UK.
Ya-Lin HuangDepartment of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK.
Stefanie KellnerDepartment of Chemistry, Ludwig-Maximilians-University Munich, Butenandtstr. 5-13, Haus F, 81377 Munich, Germany.
Susanne BornelövWellcome - MRC Cambridge Stem Cell Institute, University of Cambridge, Puddicombe Way, Cambridge CB2 0AW, UK.
Michaela FryeGerman Cancer Research Center - Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Ludwig-Maximilians-Universität München · DEUniversity of Cambridge · GBGerman Cancer Research Center · DEUniversity of Bath · GBWashington University in St. Louis · USWellcome/MRC Cambridge Stem Cell Institute · GB

Funding

Biotechnology and Biological Sciences Research CouncilCancer Research UK 15181Medical Research Council MC_PC_17230Wellcome Trust
6 · The paper itself

Abstract

The highly abundant N6-methyladenosine (m6A) RNA modification affects most aspects of mRNA function, yet the precise function of the rarer 5-methylcytidine (m5C) remains largely unknown. Here, we map m5C in the human transcriptome using methylation-dependent individual-nucleotide resolution cross-linking and immunoprecipitation (miCLIP) combined with RNA bisulfite sequencing. We identify NSUN6 as a methyltransferase with strong substrate specificity towards mRNA. NSUN6 primarily targeted three prime untranslated regions (3'UTR) at the consensus sequence motif CTCCA, located in loops of hairpin structures. Knockout and rescue experiments revealed enhanced mRNA and translation levels when NSUN6-targeted mRNAs were methylated. Ribosome profiling further demonstrated that NSUN6-specific methylation correlated with translation termination. While NSUN6 was dispensable for mouse embryonic development, it was down-regulated in human tumours and high expression of NSUN6 indicated better patient outcome of certain cancer types. In summary, our study identifies NSUN6 as a methyltransferase targeting mRNA, potentially as part of a quality control mechanism involved in translation termination fidelity.

Indexed as

RNA Processing, Post-Transcriptional3' Untranslated RegionsAnimalsBase SequenceCell Line, TumorCodon UsageConsensus SequenceCytidineEmbryonic Stem CellsGene Knockout TechniquesGenes, ReporterHEK293 CellsHumansImmunoprecipitationMethylationMice3' Untranslated Regions5-methylcytidineCytidineNSUN6 protein, humanRNA, MessengertRNA Methyltransferases

Identifiers

PMID33330931
PMCPMC7826283
OpenAlexW3111284728

What OpenQuestion holds

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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 OpenQuestion graph.