{
  "abstract": "N6-methyladenosine (m6A), one of the most abundant chemical modifications on RNA, is installed by METTL3 and several other methyltransferases, including METTL16. Although METTL16 has been characterized in several model organisms, its function in Drosophila remains unknown. Here, we show that, unlike in mammals, Drosophila Mettl16 mutants are viable but exhibit multiple developmental and behavioral defects. Both male and female mutants are sterile, with severe gametogenesis defects. Mettl16 mutant germ cells can pass the mitotic and meiotic stages, but are defective in spermatid elongation and individualization. Mettl16-GFP localizes predominantly to the nucleus, and its absence does not impair global protein synthesis in wing disc epithelial cells. MeRIP-Seq analysis indicates that Mettl16 loss affects m6A on only a small subset of transcripts, in contrast to the broad effect of Mettl3. We further demonstrate that Mettl16 interacts with U6 snRNA and is required for its m6A modification. Accordingly, Mettl16 mutants display widespread alterations in alternative splicing. Together, the pleiotropic phenotypes of Mettl16 mutants likely stem from its role in m6A deposition and U6-dependent splicing regulation of specific target transcripts. Author summary: RNA molecules carry chemical modifications that act as key regulators of their function. Among the most common is m6A, which is added by several “writer” proteins. One of these writers, Mettl16, is conserved across species, yet its in vivo role remains less understood, especially in the fruit fly Drosophila. In this study, we uncover the key functions of Mettl16 in fly development and reproduction. Flies lacking Mettl16 are viable but show a range of developmental and behavioral problems. Interestingly, both males and females are sterile, with severe defects in sperm and egg production. Mechanistically, Mettl16 only methylates a small subset of mRNAs, unlike the broad activity of the major writer Mettl3. Loss of Mettl16 reduces the m⁶A modification on U6 snRNA, a core component of the splicing machinery, and affects alternative splicing on a wide scale. We propose that the diverse defects in Mettl16 mutants arise from its role in installing m⁶A on specific transcripts and in ensuring accurate splicing through U6 modification.",
  "abstract_shown": true,
  "affiliations": [
    "State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Fudan University, Shanghai, China",
    "CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, China"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Penghui Song"
    },
    {
      "affs": [
        1
      ],
      "name": "Lijuan Ma"
    },
    {
      "name": "Dong Yan"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5c4sm3byvwaj8.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pgen.1012317",
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  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|RNA modifications and cancer"
    ],
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      "plos",
      "/Biology and life sciences/Anatomy/Reproductive system/Genital anatomy/Testes"
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      "/Biology and life sciences/Biochemistry/Nucleic acids/RNA/Non-coding RNA/Small nuclear RNA"
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      "/Biology and life sciences/Biochemistry/Nucleic acids/RNA/RNA interference"
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      "/Biology and life sciences/Genetics/Gene expression/RNA interference"
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      "/Biology and life sciences/Genetics/Genetic interference/RNA interference"
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      "/Biology and life sciences/Genetics/Phenotypes"
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      "/Biology and life sciences/Organisms/Eukaryota/Animals/Invertebrates/Arthropoda/Insects/Drosophila/Drosophila melanogaster"
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      "/Biology and life sciences/Zoology/Animals/Invertebrates/Arthropoda/Insects/Drosophila/Drosophila melanogaster"
    ],
    [
      "plos",
      "/Biology and life sciences/Zoology/Entomology/Insects/Drosophila/Drosophila melanogaster"
    ],
    [
      "plos",
      "/Medicine and health sciences/Anatomy/Reproductive system/Genital anatomy/Testes"
    ],
    [
      "plos",
      "/Research and analysis methods/Animal studies/Experimental organism systems/Animal models/Drosophila melanogaster"
    ],
    [
      "plos",
      "/Research and analysis methods/Animal studies/Experimental organism systems/Model organisms/Drosophila melanogaster"
    ],
    [
      "plos",
      "/Research and analysis methods/Model organisms/Drosophila melanogaster"
    ],
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      "plos",
      "/Research and analysis methods/Precipitation techniques/Immunoprecipitation"
    ]
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  "pdf_url": "https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1012317&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-24",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/5c4sm3byvwaj8.ris",
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    {
      "first_seen": "2026-10-30T12:17:43Z",
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  "subjects": [
    {
      "field": "biochemistry",
      "origin": "plos:gene expression",
      "subfield": "molecular-biology"
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    {
      "field": "biology",
      "origin": "plos:genetics",
      "subfield": "genetics-genomics"
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    {
      "field": "medicine",
      "origin": "plos:anatomy",
      "subfield": "physiology"
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  "title": "Role of the m⁶A methyltransferase Mettl16 in Drosophila development",
  "title_text": "Role of the m⁶A methyltransferase Mettl16 in Drosophila development",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:43Z",
  "url": "https://research.draconitic.com/paper/5c4sm3byvwaj8",
  "venue": "PLOS Genetics",
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