Skip to content
DraconiticResearch
Search Sources API
186,123 studies31 sourcesUpdated 5 min ago
Peer-reviewedCC BY 4.0Nature Communications

A human-specific microRNA controls the timing of excitatory synaptogenesis

  • Michael Soutschek1,2,3
  • Alessandra Lo Bianco2,3
  • Simon Galkin2,3
  • Tatjana Wüst2,3,4
  • Koen Wentinck1,3
  • David Colameo2,5,3
  • Tomás Germade2,6,3
  • Fridolin Groß7,2,8
  • Lukas von Ziegler9,8
  • Johannes Bohacek9,10,8,3
  • Betina Elfving11,3
  • Pierre‐Luc Germain12,9,2,1
3 more authors
  • Jochen Winterer2,3
  • Tatjana Kleele13
  • Gerhard M. Schratt14
14 affiliations
  1. 1Department of Biology, Institute of Biochemistry, ETH Zurich, Zurich, Switzerland
  2. 2Laboratory of Systems Neuroscience, Institute for Neuroscience, Department of Health Science and Technology, ETH Zurich, Zurich, Switzerland
  3. 3Laboratory of Systems Neuroscience, Institute for Neuroscience, Department of Health Science and Technology, ETH Zürich, Switzerland
  4. 4Ncardia Services B.V., Leiden, The Netherlands
  5. 5Laboratory of Epigenetics and Neuroendocrinology, Institute for Neuroscience, Department of Health Science and Technology, ETH Zürich, Switzerland
  6. 6CNRS UMR514 ImmunoConcEpT, University of Bordeaux, France
  7. 7CNRS UMR5164 ImmunoConcEpT, University of Bordeaux, Bordeaux, France
  8. 8Laboratory of Molecular and Behavioural Neuroscience, Institute for Neuroscience, Department of Health Science and Technology, ETH Zürich, Switzerland
  9. 9Laboratory of Molecular and Behavioural Neuroscience, Institute for Neuroscience, Department of Health Science and Technology, ETH Zurich, Zurich, Switzerland
  10. 10Lab of Statistical Bioinformatics, IMLS, University of Zürich, Switzerland
  11. 11Translational Neuropsychiatry Unit A601, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
  12. 12Lab of Statistical Bioinformatics, IMLS, University of Zurich, Zurich, Switzerland
  13. 13Department of Biology, Institute of Biochemistry, ETH Zurich, Zurich, Switzerland. [email protected]
  14. 14Laboratory of Systems Neuroscience, Institute for Neuroscience, Department of Health Science and Technology, ETH Zurich, Zurich, Switzerland. [email protected]
Open at sourcePDFDOICite

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.

Related

  1. Activity-driven synaptic translocation of LGI1 controls excitatory neurotransmission
    Ulku Cuhadar, Lorenzo Calzado-Reyes, Carlos Pascual-Caro +10
    Cell ReportsPeer-reviewedCC BY-NC16 citedNeuroscienceHAL
  2. Sex-specific long-term alteration of hippocampal excitation/inhibition balance and behavior by transient caffeine exposure during synaptogenesis
    S. Rimbert, J. Pressey, F. Gomez-Castro +5
    bioRxivPreprintCC BY-NDFull textNeurosciencebioRxiv
  3. Transcriptomic profiling reveals estradiol and progesterone specific microRNA signatures differentially regulate mRNA targets in vaginal epithelial cells
    S. Joshi, A. Nazli, C. Verschoor +1
    bioRxivPreprintAll rights reservedFull textImmunologybioRxiv
  4. A Specific Population of Reticulospinal Neurons Controls the Termination of Locomotion
    Laurent Juvin, Swantje Grätsch, Emilie Trillaud-Doppia +3
    Cell ReportsPeer-reviewedCC BYFull text73 citedNeuroscienceHAL
  5. A subtype-specific gene regulatory program controls differential circuit integration of deep CA3 pyramidal neurons
    J. de Wit, D. Daaboul, J. Vandensteen +17
    bioRxivPreprintCC BY-NC-NDFull textNeurosciencebioRxiv

Cite

BibTeXRIS
BibTeX
@article{soutschek2026humanspecific,
  title = {{A human-specific microRNA controls the timing of excitatory synaptogenesis}},
  author = {Michael Soutschek and Alessandra Lo Bianco and Simon Galkin and Tatjana Wüst and Koen Wentinck and David Colameo and Tomás Germade and Fridolin Groß and Lukas von Ziegler and Johannes Bohacek and Betina Elfving and Pierre‐Luc Germain and Jochen Winterer and Tatjana Kleele and Gerhard M. Schratt},
  journal = {Nature Communications},
  year = {2026},
  month = jul,
  doi = {10.1038/s41467-026-74753-y},
  url = {https://u-bordeaux.hal.science/hal-05737556v1},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - A human-specific microRNA controls the timing of excitatory synaptogenesis
AU  - Michael Soutschek
AU  - Alessandra Lo Bianco
AU  - Simon Galkin
AU  - Tatjana Wüst
AU  - Koen Wentinck
AU  - David Colameo
AU  - Tomás Germade
AU  - Fridolin Groß
AU  - Lukas von Ziegler
AU  - Johannes Bohacek
AU  - Betina Elfving
AU  - Pierre‐Luc Germain
AU  - Jochen Winterer
AU  - Tatjana Kleele
AU  - Gerhard M. Schratt
PY  - 2026
DA  - 2026/07/06
JO  - Nature Communications
DO  - 10.1038/s41467-026-74753-y
UR  - https://u-bordeaux.hal.science/hal-05737556v1
AB  - 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.
SN  - 2041-1723
SN  - 2041-1723
ER  -