{
  "abstract": "Neural circuit development in the human cortex is considerably prolonged in comparison to non-human primates, a trait that contributes to the remarkable cognitive capacity of modern humans. Here, we explore the regulatory role of non-coding RNAs, which dramatically expanded during brain evolution, in synapse development of human induced pluripotent stem-cell derived neurons. We found that inhibition of a human-specific microRNA, miR-1229-3p, alters the trajectory of human neuronal maturation and enhances excitatory synaptic transmission. Transcriptome analysis following miR-1229 knockdown revealed a downregulation of mitochondrial DNA (mtDNA) encoded genes. We further show that miR-1229 regulates mitochondrial morphology, mtDNA abundance as well as mitophagy, and that stimulation of mitochondrial metabolism rescues decreased calcium buffering in miR-1229-3p depleted neurons. Accordingly, miR-1229 directly targets an entire network of genes involved in mitochondrial function and ER-associated protein homeostasis. Our findings reveal an important function of human-specific miR-1229-3p in developmental timing of human synaptogenesis and generally implicate non-coding RNAs in the control of human connectivity and cognition.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Biology, Institute of Biochemistry, ETH Zurich, Zurich, Switzerland",
    "Laboratory of Systems Neuroscience, Institute for Neuroscience, Department of Health Science and Technology, ETH Zurich, Zurich, Switzerland",
    "Laboratory of Systems Neuroscience, Institute for Neuroscience, Department of Health Science and Technology, ETH Zürich, Switzerland",
    "Ncardia Services B.V., Leiden, The Netherlands",
    "Laboratory of Epigenetics and Neuroendocrinology, Institute for Neuroscience, Department of Health Science and Technology, ETH Zürich, Switzerland",
    "CNRS UMR514 ImmunoConcEpT, University of Bordeaux, France",
    "CNRS UMR5164 ImmunoConcEpT, University of Bordeaux, Bordeaux, France",
    "Laboratory of Molecular and Behavioural Neuroscience, Institute for Neuroscience, Department of Health Science and Technology, ETH Zürich, Switzerland",
    "Laboratory of Molecular and Behavioural Neuroscience, Institute for Neuroscience, Department of Health Science and Technology, ETH Zurich, Zurich, Switzerland",
    "Lab of Statistical Bioinformatics, IMLS, University of Zürich, Switzerland",
    "Translational Neuropsychiatry Unit A601, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark",
    "Lab of Statistical Bioinformatics, IMLS, University of Zurich, Zurich, Switzerland",
    "Department of Biology, Institute of Biochemistry, ETH Zurich, Zurich, Switzerland. tatjana.kleele@biol.ethz.ch",
    "Laboratory of Systems Neuroscience, Institute for Neuroscience, Department of Health Science and Technology, ETH Zurich, Zurich, Switzerland. gerhard.schratt@hest.ethz.ch"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Michael Soutschek",
      "orcid": "0000-0002-8472-8124"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Alessandra Lo Bianco",
      "orcid": "0000-0001-6408-8003"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Simon Galkin",
      "orcid": "0000-0003-0479-0591"
    },
    {
      "affs": [
        1,
        2,
        3
      ],
      "name": "Tatjana Wüst"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Koen Wentinck"
    },
    {
      "affs": [
        1,
        4,
        2
      ],
      "name": "David Colameo",
      "orcid": "0000-0001-8432-9396"
    },
    {
      "affs": [
        1,
        5,
        2
      ],
      "name": "Tomás Germade",
      "orcid": "0000-0002-5144-1266"
    },
    {
      "affs": [
        6,
        1,
        7
      ],
      "name": "Fridolin Groß",
      "orcid": "0000-0003-4964-8062"
    },
    {
      "affs": [
        8,
        7
      ],
      "name": "Lukas von Ziegler",
      "orcid": "0000-0002-5942-7928"
    },
    {
      "affs": [
        8,
        9,
        7,
        2
      ],
      "name": "Johannes Bohacek",
      "orcid": "0000-0002-8442-653X"
    },
    {
      "affs": [
        10,
        2
      ],
      "name": "Betina Elfving",
      "orcid": "0000-0001-6939-5088"
    },
    {
      "affs": [
        11,
        8,
        1,
        0
      ],
      "name": "Pierre‐Luc Germain",
      "orcid": "0000-0003-3418-4218"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Jochen Winterer",
      "orcid": "0000-0002-6800-6594"
    },
    {
      "affs": [
        12
      ],
      "name": "Tatjana Kleele",
      "orcid": "0000-0001-5320-7337"
    },
    {
      "affs": [
        13
      ],
      "name": "Gerhard M. Schratt",
      "orcid": "0000-0001-7527-2025"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2j60bvnder3g7.bib",
  "cited_by": 10,
  "doi": "10.1038/s41467-026-74753-y",
  "fulltext_url": null,
  "id": "2j60bvnder3g7",
  "issns": [
    "2041-1723",
    "2041-1723"
  ],
  "landing_url": "https://u-bordeaux.hal.science/hal-05737556v1",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
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  "pdf_url": "https://u-bordeaux.hal.science/hal-05737556/document",
  "pmcid": "PMC13473650",
  "pmid": "42409844",
  "published": "2026-07-06",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/2j60bvnder3g7.ris",
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      "first_seen": "2026-10-30T12:17:27Z",
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  "subjects": [
    {
      "field": "biology",
      "origin": "hal:1.sdv.imm",
      "subfield": "immunology"
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  "title": "A human-specific microRNA controls the timing of excitatory synaptogenesis",
  "title_text": "A human-specific microRNA controls the timing of excitatory synaptogenesis",
  "type": "peer-reviewed",
  "updated_at": "2026-11-04T13:21:07Z",
  "url": "https://research.draconitic.com/paper/2j60bvnder3g7",
  "venue": "Nature Communications",
  "versions": []
}