Evidence map›Paper›PMID 34673944›Full record

ArticleHuman molecular genetics2022

C/D box snoRNA SNORD113-6/AF357425 plays a dual role in integrin signalling and arterial fibroblast function via pre-mRNA processing and 2'O-ribose methylation.

Eva van Ingen, Daphne A L van den Homberg, M Leontien van der Bent, Hailiang Mei, Nikolina Papac-Milicevic, Veerle Kremer, Reinier A Boon, Paul H A Quax, Johann Wojta, A Yaël Nossent

Open access · hybridAbstract read
In one paragraph

Article in Human molecular genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.6field-weighted citation impact, top 18% 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

16 citing papers in PubMed, 23 citations in OpenAlex.

  1. The dark genome in cardiovascular medicine.European heart journal · 2026
    Review
  2. Article
  3. Review
  4. Genome-wide profiling of RNA 2'-bioRxiv : the preprint server for biology · 2025
    Article
  5. snoCLASH Reveals Extensive snoRNA-mRNA Interaction Networks.bioRxiv : the preprint server for biology · 2025
    Article
  6. Review
  7. Review
  8. Identification of FBLL1 as a neuron-specific RNA 2'-O-methyltransferase mediating neuronal differentiation.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  9. Review
  10. Review
  11. Review
  12. Review
  13. Review
  14. Article
  15. Article
  16. 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

10 authors at 5 institutions in 3 countries.

Eva van IngenDepartment of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
Daphne A L van den HombergDepartment of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
M Leontien van der BentDepartment of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
Hailiang MeiBiomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands.
Nikolina Papac-MilicevicDepartment of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
Veerle KremerDepartment of Physiology, Amsterdam Cardiovascular Sciences, Vrije Universiteit, Amsterdam UMC location VUMC, Amsterdam, The Netherlands.
Reinier A BoonDepartment of Physiology, Amsterdam Cardiovascular Sciences, Vrije Universiteit, Amsterdam UMC location VUMC, Amsterdam, The Netherlands.
Paul H A QuaxDepartment of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
Johann WojtaDepartment of Internal Medicine II, Medical University of Vienna, Vienna, Austria.
A Yaël NossentDepartment of Surgery, Leiden University Medical Center, Leiden, The Netherlands.ORCID 0000-0002-2155-4286
Leiden University Medical Center · NLAmsterdam University Medical Centers · NLGoethe University Frankfurt · DELudwig Boltzmann Institute for Cancer Research · ATMedical University of Vienna · AT

Funding

Austrian Science Fund FWF M 2578
6 · The paper itself

Abstract

We have previously shown that C/D box small nucleolar RNAs (snoRNAs) transcribed from the DLK1-DIO3 locus on human chromosome 14 (14q32) are associated with cardiovascular disease. DLK1-DIO3 snoRNAs are 'orphan snoRNAs' that have no known targets. We aimed to identify RNA targets and elucidate the mechanism-of-action of human SNORD113-6 (AF357425 in mice). As AF357425-knockout cells were non-viable, we induced overexpression or inhibition of AF357425 in primary murine fibroblasts and performed RNA-Seq. We identified several pre-mRNAs with conserved AF357425/SNORD113-6 D'-seed binding sites in the last exon/3' untranslated region (3'UTR), which directed pre-mRNA processing and splice-variant-specific protein expression. We also pulled down the snoRNA-associated methyltransferase fibrillarin from AF357425-High versus AF357425-Low fibroblast lysates, followed by RNA isolation, ribosomal RNA depletion and RNA-Seq. Identifying mostly mRNAs, we subjected these to PANTHER pathway analysis and observed enrichment for genes in the integrin pathway. We confirmed 2'O-ribose methylation in six integrin pathway mRNAs (MAP2K1, ITGB3, ITGA7, PARVB, NTN4 and FLNB). Methylation and mRNA expressions were decreased while mRNA degradation was increased under AF357425/SNORD113-6 inhibition in both murine and human primary fibroblasts, but effects on protein expression were more ambiguous. Integrin signalling is crucial for cell-cell and cell-matrix interactions, and correspondingly, we observed altered human primary arterial fibroblast function upon SNORD113-6 inhibition.

Indexed as

RNA PrecursorsRNA, Small NucleolarAnimalsFibroblastsIntegrinsMethylationMiceRiboseIntegrinsRiboseRNA PrecursorsRNA, Small Nucleolar

Identifiers

PMID34673944
PMCPMC8976432
OpenAlexW3206425665

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Registered trials

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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.