| First Author | Takeuchi A | Year | 2018 |
| Journal | Cell Rep | Volume | 23 |
| Issue | 5 | Pages | 1326-1341 |
| PubMed ID | 29719248 | Mgi Jnum | J:271630 |
| Mgi Id | MGI:6279047 | Doi | 10.1016/j.celrep.2018.03.141 |
| Citation | Takeuchi A, et al. (2018) Loss of Sfpq Causes Long-Gene Transcriptopathy in the Brain. Cell Rep 23(5):1326-1341 |
| abstractText | 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 dysregulation 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. |
