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Although several RNA\u2010binding proteins (RBPs) were shown to shuttle miRNAs to EVs, how they are loaded with miRNA is unknown. This study demonstrates that the core accessory protein of the cytoplasmic miRNA production machinery TRBP interacts with several EV\u2010RBPs and differentially regulates miRNA secretion in small EVs. TRBP\u2010regulated EV\u2010miRNAs were highly enriched in a Syncrip\u2010recognition sequence motif. Moreover, we show that Syncrip associates with TRBP via its C\u2010terminal domain at the surface of the endoplasmic reticulum (ER), a nucleation site of the miRNA production machinery. The recruitment of Syncrip to ER\u2010associated TRBP was regulated by ER\u2010endosome membrane contact sites (MCS), whereby increased MCS formation promotes Syncrip loading to endosomes as well as Argonaute 2\u2010positive RNA granules. Functionally, this pathway is important for the regulation of synapse formation in developing neurons, as expression of miRNA\u2010 or TRBP\u2010binding deficient mutants of Syncrip differentially regulated synapse formation in EV\u2010donor and recipient neurons. Overall, this work highlights an important role of TRBP as a gatekeeper for microRNA sorting, which could be crucial for the fine\u2010tuning of neuronal circuits during postnatal development.<\/jats:p>","DOI":"10.1002\/advs.78067","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:56:09Z","timestamp":1790801769000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Cytoplasmic MicroRNA\u2010Production Complex Regulates MicroRNA Sorting to Extracellular Vesicles During Synaptogenesis"],"prefix":"10.1002","author":[{"given":"Yuzhou","family":"Zeng","sequence":"first","affiliation":[{"name":"Department of Old Age Psychiatry and Cognitive Disorders University of Bonn Medical Center Bonn Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE)  Bonn 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