GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE244nnn/GSE244444/primary200OKTranscriptomicsHomo sapiens Non-coding RNA profiling by high throughput sequencingExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE244444GEOGSEfalseA human-specific microRNA controls the timing of excitatory synaptogenesisNeural 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. This SuperSeries is composed of the SubSeries listed below.2025/10/30GSE244444GSM7816238GSM7816239GSM7816232GSM7816199GSM7816233GSM7816197GSM7816230GSM7816198GSM7816231GSM7816236GSM7816237GSM9304009GSM9304008GSM7816234GSM9304007GSM7816235GSM9304006GSM7816191GSM7816192GSM7816190GSM7816195GSM7816196GSM7816193GSM7816194GSM7816207GSM7816208GSM7816205GSM7816206GSM7816209GSM7816200GSM7816241GSM7816242GSM7816203GSM7816204GSM7816201GSM7816202GSM9304014GSM9304013GSM7816240GSM9304012GSM9304011GSM9304010GSM7816177GSM7816178GSM7816175GSM7816176GSM7816179GSM7816170GSM7816173GSM7816174GSM7816171GSM7816172GSM7816229GSM7816227GSM7816228GSM7816188GSM7816189GSM7816222GSM7816186GSM7816187GSM7816225GSM7816226GSM7816223GSM7816224GSM7816180GSM7816181GSM7816184GSM7816185GSM7816182GSM78161831857324676244444Homo sapiens