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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,9,9]]},"abstract":"<jats:p>\n                    The RNA-binding protein TRIM71 is essential for brain development, and recent genetic studies in humans have identified\n                    <jats:italic toggle=\"yes\">TRIM71<\/jats:italic>\n                    as a risk gene for congenital hydrocephal-us (CH). Here, we show that monoallelic missense mutations in\n                    <jats:italic toggle=\"yes\">TRIM71<\/jats:italic>\n                    are associated with hearing loss (HL) and inner ear aplasia in humans. Utilizing conditional\n                    <jats:italic toggle=\"yes\">Trim71<\/jats:italic>\n                    knockout mice carrying a CH and HL-associated mutation, we demonstrate that loss of TRIM71 function during early otic development (embryonic day 9 to 10) causes severe HL. While inner ear morphogenesis occurs normally in\n                    <jats:italic toggle=\"yes\">Trim71<\/jats:italic>\n                    knockout mice, we find that early otic loss of TRIM71 function disrupts the highly stereotyped timing of cell cycle exit and differentiation within the inner ear auditory sensory organ (cochlea), resulting in the premature formation and innervation of mechanosensory hair cells. Transcriptomic profiling of\n                    <jats:italic toggle=\"yes\">Trim71<\/jats:italic>\n                    -deficient cochlear progenitor cells identifies\n                    <jats:italic toggle=\"yes\">Inhba<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">Tgfbr2<\/jats:italic>\n                    as targets of TRIM71 repression, and our analysis of\n                    <jats:italic toggle=\"yes\">Inhba-Tgfbr1<\/jats:italic>\n                    double knockout mice indicates that TRIM71 maintains hair cell progenitors in a proliferative and undifferentiated state by restricting TGF\u03b2-type signaling. Characterization of hair cells and their associated neurons in adult\n                    <jats:italic toggle=\"yes\">Trim71<\/jats:italic>\n                    knockout mice revealed reduced presynaptic terminals and neuronal degeneration in the outer hair cell region, providing a basis for the observed hearing deficits in\n                    <jats:italic toggle=\"yes\">Trim71<\/jats:italic>\n                    knockout mice.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2505811122","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T18:00:10Z","timestamp":1756836010000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":4,"title":["The RNA-binding protein TRIM71 is essential for hearing in humans and mice and times auditory sensory organ development"],"prefix":"10.1073","volume":"122","author":[{"given":"Xiao-Jun","family":"Li","sequence":"first","affiliation":[{"name":"The Solomon H. 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