PXD045809-1

PXD045809 is an original dataset announced via ProteomeXchange.

Title	A human-specific microRNA controls the timing of excitatory synaptogenesis
Description	The development of neural circuits in the human cortex is considerably prolonged in comparison to non-human primates, a trait which contributes to the remarkable cognitive capacity of modern humans. In contrast to protein-coding genes, non-coding genes underwent a dramatic expansion during evolution, suggesting their involvement in human-specific aspects of brain development. Here, using a glial free human-induced pluripotent stem-cell derived neuron model (“igNeurons”), we show widespread expression and dynamic regulation of various non-coding RNA classes, including microRNAs, during human excitatory synapse development. The expression of a human-specific microRNA, miR-1229-3p, strongly correlates with the neuromorphological trajectory of igNeurons. miR-1229-3p inhibition promotes the formation of excitatory synaptic co-clusters at early stages but reduces dendritic arborization in more mature neurons, consistent with accelerated neuronal maturation. Morphological alterations are accompanied by enhanced calcium spike activity and excitatory synaptic transmission. Mechanistically, miR-1229-3p controls mitochondrial homeostasis by directly targeting important regulators of mitochondrial autophagy and fission, such as Pink1. Stimulation of mitochondrial metabolism rescues the enhanced calcium spike activity in miR-1229-3p depleted neurons, demonstrating a causal involvement of mitochondrial homeostasis. Thus, 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.
HostingRepository	PRIDE
AnnounceDate	2025-11-03
AnnouncementXML	Submission_2025-11-03_02:16:35.233.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Michael Soutschek
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-29 05:45:55	ID requested
⏵ 1	2025-11-03 02:16:35	announced

Dataset with its publication pending

submitter keyword: neuron, development, human,iPSC

Gerhard Schratt
contact affiliation	ETH Zurich, D-HEST, Lab of Systems Neuroscience
contact email	gerhard.schratt@hest.ethz.ch
lab head
Michael Soutschek
contact affiliation	ETH Zurich
contact email	michael.soutschek@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD045809
     1. Label: PRIDE project
     2. Name: A human-specific microRNA controls the timing of excitatory synaptogenesis