Most of the genes that are expressed in neuron-specific manner have extremely long introns, such that the total gene length often exceeds 100kb. It is not clear why these genes need to be so long. We recently discovered a new mechanism controlling the expression of long genes, which links the choice of alternative promoters to alternative splicing, enabling a greater diversity of alternative isoforms to be produced in different regions of the brain. Here, a combination of computational, genomic, genetic and cell biology will be used to examine the role of this mechanism for the differentiation of different neuronal types.
Burnette JM, Miyamoto-Sato E, Schaub MA, Conklin J, Lopez AJ.Subdivision of large introns in Drosophila by recursive splicing at nonexonic elements. Genetics. 2005 Jun;170(2):661-74.
King IF, Yandava CN, Mabb AM, Hsiao JS, Huang HS, Pearson BL, Calabrese JM, Starmer J, Parker JS, Magnuson T, Chamberlain SJ, Philpot BD, Zylka MJ.Topoisomerases facilitate transcription of long genes linked to autism. Nature. 2013 Sep 5;501(7465):58-62.
Lagier-Tourenne C et alDivergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs. Nat Neurosci. 2012 Nov;15(11):1488-97
Shepard S, McCreary M, Fedorov A.The peculiarities of large intron splicing in animals. PLoS One. 2009 Nov 16;4(11):e7853
Zarnack K, König J, Tajnik M, Martincorena I, Eustermann S, Stévant I, Reyes A, Anders S, Luscombe NM, Ule J.Direct competition between hnRNP C and U2AF65 protects the transcriptome from the exonization of Alu elements. Cell. 2013 Jan 31;152(3):453-66.