Transcriptomics

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A human-specific microRNA controls the timing of excitatory synaptogenesis (miRNA mimics)


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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE310579 | GEO | 2026/06/22

REPOSITORIES: GEO

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GSE310579_SY5Y_DEA_10nM.csv.gz Csv
GSE310579_SY5Y_DEA_20nM.csv.gz Csv
GSE310579_SY5Y_DEA_combined.csv.gz Csv
GSE310579_SY5Y_counts.csv.gz Csv
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