Nature communicationsJul 6, 2026

A human-specific microRNA controls the timing of forming excitatory brain connections

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jul 7, 2026

Abstract

Inhibition of the human-specific microRNA, miR-1229-3p, alters the trajectory of neuronal maturation in human-derived neurons.

Inhibition of miR-1229-3p enhances excitatory synaptic transmission in human neurons.
Transcriptome analysis shows downregulation of genes encoded by mitochondrial DNA following miR-1229 knockdown.
miR-1229 is involved in regulating mitochondrial shape, mitochondrial DNA levels, and the process of removing damaged mitochondria.
Increased mitochondrial metabolism can restore calcium buffering in neurons lacking miR-1229-3p.
miR-1229 directly influences a network of genes that are critical for mitochondrial function and protein management within the cell.

Simplified

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.

Full Text

Full text is available at the source.

View Full Text ↗

Funding

Competing interests

Competing interests: The authors declare no competing interests.

PubMed

A human-specific microRNA controls the timing of forming excitatory brain connections

Abstract

Full Text

Funding

Competing interests

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the longevity & aging brief