Evidence map›Paper›PMID 40637237›Full record

ArticleNucleic acids research2025

Nucleolar FRG2 lncRNAs inhibit rRNA transcription and cytoplasmic translation, linking FSHD to dysregulation of muscle-specific protein synthesis.

Valentina Salsi, Francesca Losi, Bruno Fosso, Marco Ferrarini, Sara Pini, Marcello Manfredi, Gaetano Vattemi, Tiziana Mongini, Lorenzo Maggi, Graziano Pesole and 4 more

Erratum issuedAbstract read
In one paragraph

Article in Nucleic acids research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Novel biomarkers for sarcopenia: a narrative review.Journal of orthopaedic surgery and research · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Valentina SalsiDepartment of Biomedical, Metabolic and Neural Sciences University of Modena and Reggio Emilia, Modena 41125, Italy.
Francesca LosiDepartment of Biomedical, Metabolic and Neural Sciences University of Modena and Reggio Emilia, Modena 41125, Italy.
Bruno FossoDepartment of Biosciences, Biotechnology and Environment, University of Bari A. Moro, Bari 70121, Italy.ORCID 0000-0003-2324-086X
Marco FerrariniDepartment of Biomedical, Metabolic and Neural Sciences University of Modena and Reggio Emilia, Modena 41125, Italy.
Sara PiniDepartment of Biomedical, Metabolic and Neural Sciences University of Modena and Reggio Emilia, Modena 41125, Italy.
Marcello ManfrediDepartment of Translational Medicine, University of Piemonte Orientale, Novara 28100, Italy.
Gaetano VattemiDepartment of Neurosciences, Biomedicine and Movement Sciences, Section of Clinical Neurology, University of Verona, Verona 37134, Italy.
Tiziana MonginiDepartment of Neurosciences "Rita Levi Montalcini", Center for Neuromuscular Diseases, University of Turin, Turin 10124, Italy.
Lorenzo MaggiNeuroimmunology and Neuromuscular Diseases Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan 20133, Italy.
Graziano PesoleDepartment of Biosciences, Biotechnology and Environment, University of Bari A. Moro, Bari 70121, Italy.ORCID 0000-0003-3663-0859
Anthony K HenrasMolecular, Cellular and Developmental Biology Unit (MCD), Centre for Integrative Biology (CBI), University of Toulouse, CNRS, UPS, Toulouse 31400, France.
Paul D KaufmanDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, United States.
Brian McStayCentre for Chromosome Biology, College of Science and Engineering, University of Galway, Galway H91 W2TY, Ireland.
Rossella TuplerDepartment of Biomedical, Metabolic and Neural Sciences University of Modena and Reggio Emilia, Modena 41125, Italy.ORCID 0000-0002-3797-1789

Funding

Cell Biology of Mammalian NucleiR35GM152201 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI PAUL D. KAUFMAN · 2024 to 2026
$1.3M
Cariplo-Telethon Alliance GJC23060Departments of ExcellenceEuropean Union -NextGenerationEUFSHD Global Research FoundationINNOVA EJ-2022-23683266INNOVA IR0000010Italian Ministry of UniversityNIGMS NIH HHS R35 GM152201NIH HHS 1NIH HHS R35 GM15220NIH HHS RO1NS0475840NIH HHS U01 CA260669Research under PNRR E93C22001860006Research under PNRR M4C2-I1.3Research under PNRR PE_00000019University of Modena and Reggio Emilia
6 · The paper itself

Abstract

Facioscapulohumeral muscular dystrophy (FSHD) is a hereditary myopathy linked to deletions of the tandemly arrayed D4Z4 macrosatellite at human chromosome 4q35. These deletions cause local chromatin changes and anomalous expression of nearby transcripts FRG2A, DBET, and D4Z4. We discovered that FRG2A is part of a family of long noncoding RNAs (lncRNAs) expressed in skeletal muscle cells, with levels varying among patients. FRG2A localizes in the nucleolus and associates with repetitive DNA at ribosomal DNA (rDNA) loci and centromeres. Elevated FRG2A expression in FSHD cells alters the three-dimensional architecture of heterochromatin at the nucleolar periphery and reduces rDNA transcription and translation rates, resulting in decreased synthesis of skeletal muscle proteins. We also show that myoblasts from FSHD patients display reduced synthesis of skeletal muscle proteins during differentiation. Our results support a disease model in which nucleolar accumulation of D4Z4-driven lncRNA impairs protein synthesis and contributes to muscle wasting.

Indexed as

Muscle ProteinsMuscular Dystrophy, FacioscapulohumeralProtein BiosynthesisRNA, Long NoncodingRNA, RibosomalTranscription, GeneticCell NucleolusDNA, RibosomalHumansMuscle, SkeletalMyoblastsDNA, RibosomalMuscle ProteinsRNA, Long NoncodingRNA, Ribosomal

Identifiers

PMID40637237
PMCPMC12242771

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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.