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Here we report the molecular and genetic characterization of Integrator complex subunit 15 (INTS15). INTS15 was identified in search for the causative gene(s) for an autosomal-dominant eye disease with variable individual manifestation found in a large pedigree. While homozygous Ints15 knockout mice are embryonic lethal, mutant mice lacking a small C-terminal region of Ints15 show ocular malformations similar to the human patients. INTS15 is highly expressed in the eye and brain during embryogenesis and stably interacts with the Integrator complex to support small nuclear RNA 3\u2032 end processing. Its knockdown resulted in missplicing of a large number of genes, probably as a secondary consequence, and substantially affected genes associated with eye and brain development. Moreover, studies using human iPS cells-derived neural progenitor cells showed that INTS15 is critical for axonal outgrowth in retinal ganglion cells. This study suggests a new link between general transcription machinery and a highly specific hereditary disease.<\/jats:p>","DOI":"10.1093\/hmg\/ddad034","type":"journal-article","created":{"date-parts":[[2023,2,28]],"date-time":"2023-02-28T06:30:59Z","timestamp":1677565859000},"page":"2032-2045","source":"Crossref","is-referenced-by-count":17,"title":["Integrator complex subunit 15 controls mRNA splicing and is critical for eye development"],"prefix":"10.1093","volume":"32","author":[{"given":"Noriyuki","family":"Azuma","sequence":"first","affiliation":[{"name":"National Centre for Child Health and Development Department of Ophthalmology and Laboratory for Visual Science, , Tokyo 157-8535 , Japan"},{"name":"Tokyo Medical and Dental University (TMDU) Department of Developmental and Regenerative Biology, Medical Research Institute, , Tokyo 113-8510 , 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