Journal
CELL REPORTS
Volume 23, Issue 5, Pages 1326-1341Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2018.03.141
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Funding
- Ministry of Education, Culture, Sports, Science, and Technology of Japan (MEXT, JSPS KAKENHI) [19500269, 25500288, 21249013, 15H05721]
- Japan Science and Technology Agency (JST)
- Japan Agency for Medical Research and Development (AMED)
- Asian CORE Program of JSPS
- iCeMS Cross-Disciplinary Research Promotion Project of Kyoto University
- Fujiwara Memorial Foundation
- Grants-in-Aid for Scientific Research [21249013, 15H05721, 19500269] Funding Source: KAKEN
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Genes specifically expressed in neurons contain members with extended long introns. Longer genes present a problem with respect to fulfilment of gene length transcription, and evidence suggests that dys-regulation of long genes is a mechanism underlying neurodegenerative and psychiatric disorders. Here, we report the discovery that RNA-binding protein Sfpq is a critical factor for maintaining transcriptional elongation of long genes. We demonstrate that Sfpq co-transcriptionally binds to long introns and is required for sustaining long-gene transcription by RNA polymerase II through mediating the interaction of cyclin-dependent kinase 9 with the elongation complex. Phenotypically, Sfpq disruption caused neuronal apoptosis in developing mouse brains. Expression analysis of Sfpq-regulated genes revealed specific downregulation of developmentally essential neuronal genes longer than 100 kb in Sfpq-disrupted brains; those genes are enriched in associations with neurodegenerative and psychiatric diseases. The identified molecular machinery yields directions for targeted investigations of the association between long-gene transcriptopathy and neuronal diseases.
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