ArticleProceedings of the National Academy of Sciences of the United States of America2016
MRG15 is required for pre-mRNA splicing and spermatogenesis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 106 citations in OpenAlex.
- lncRNA-operated stem cell fate control: RPS3 mediates the in situ Gm16751-Zhx3 interactome to program spermatogonial stem cell differentiation.Cell & bioscience · 2026Article
- SETD2 methyltransferase activity promotes correct transcription initiation and termination.EMBO reports · 2026Article
- Review
- The multitalented TIP60 chromatin remodeling complex: wearing many hats in epigenetic regulation, cell division and diseases.Epigenetics & chromatin · 2025Review
- MRG15 alternative splicing regulates CDK1 transcriptional activity in mouse cell senescence and myocardial regeneration.Communications biology · 2025Article
- Characterization of PRDM9 Multifunctionality in Yak Testes Through Protein Interaction Mapping.International journal of molecular sciences · 2025Article
- Kdm2a inhibition in skeletal muscle improves metabolic flexibility in obesity.Nature metabolism · 2025Article
- MRG15 promotes cell apoptosis through inhibition of mitophagy in hyperlipidemic acute pancreatitis.Apoptosis : an international journal on programmed cell death · 2025Article
- CARF regulates the alternative splicing and piwi/piRNA complexes during mouse spermatogenesis through PABPC1.Acta biochimica et biophysica Sinica · 2024Article
- The Intricate Functional Networks of Pre-mRNA Alternative Splicing in Mammalian Spermatogenesis.International journal of molecular sciences · 2024Review
- The role of HnrnpF/H as a driver of oligoteratozoospermia.iScience · 2024Article
- Loss of function of male-specific lethal 3 (Msl3) does not affect spermatogenesis in rodents.Developmental dynamics : an official publication of the American Association of Anatomists · 2024Article
- Structural and functional insights into the epigenetic regulator MRG15.Acta pharmacologica Sinica · 2024Review
- Uncovering a multitude of stage-specific splice variants and putative protein isoforms generated along mouse spermatogenesis.BMC genomics · 2024Article
- SIN-3 acts in distinct complexes to regulate the germline transcriptional program in Caenorhabditis elegans.Development (Cambridge, England) · 2023Article
- The arginine methyltransferase Prmt1 coordinates the germline arginine methylome essential for spermatogonial homeostasis and male fertility.Nucleic acids research · 2023Article
- SRSF2 is required for mRNA splicing during spermatogenesis.BMC biology · 2023Article
- Identifying Molecular Roadblocks for Transcription Factor-Induced Cellular Reprogramming In Vivo by UsingJournal of developmental biology · 2023Review
- BCAS2 regulates granulosa cell survival by participating in mRNA alternative splicing.Journal of ovarian research · 2023Article
- Tip60/KAT5 Histone Acetyltransferase Is Required for Maintenance and Neurogenesis of Embryonic Neural Stem Cells.International journal of molecular sciences · 2023Article
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
Splicing can be epigenetically regulated and involved in cellular differentiation in somatic cells, but the interplay of epigenetic factors and the splicing machinery during spermatogenesis remains unclear. To study these interactions in vivo, we generated a germline deletion of MORF-related gene on chromosome 15 (MRG15), a multifunctional chromatin organizer that binds to methylated histone H3 lysine 36 (H3K36) in introns of transcriptionally active genes and has been implicated in regulation of histone acetylation, homology-directed DNA repair, and alternative splicing in somatic cells. Conditional KO (cKO) males lacking MRG15 in the germline are sterile secondary to spermatogenic arrest at the round spermatid stage. There were no significant alterations in meiotic division and histone acetylation. Specific mRNA sequences disappeared from 66 germ cell-expressed genes in the absence of MRG15, and specific intronic sequences were retained in mRNAs of 4 genes in the MRG15 cKO testes. In particular, introns were retained in mRNAs encoding the transition proteins that replace histones during sperm chromatin condensation. In round spermatids, MRG15 colocalizes with splicing factors PTBP1 and PTBP2 at H3K36me3 sites between the exons and single intron of transition nuclear protein 2 (Tnp2). Thus, our results reveal that MRG15 is essential for pre-mRNA splicing during spermatogenesis and that epigenetic regulation of pre-mRNA splicing by histone modification could be useful to understand not only spermatogenesis but also, epigenetic disorders underlying male infertile patients.
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