Authors
Michael Soutschek, Alessandra Lo Bianco, Simon Galkin, Tatjana Wüst, Koen Wentinck, David Colameo, Tomas Germade, Fridolin Gross, Lukas von Ziegler, Johannes Bohacek, Betina Elfving, Pierre-Luc Germain, Jochen Winterer, Tatjana Kleele, Gerhard Schratt
Published in
Nature communications. Jul 06, 2026. Epub Jul 06, 2026.
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.
PMID:
42409844
Bibliographic data and abstract were imported from PubMed on 07 Jul 2026.
Read full publication at:
Please sign in
to see all details.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 11
- Comments 0