RT Journal Article
SR Electronic
T1 Precise temporal regulation of alternative splicing during neural development
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 247601
DO 10.1101/247601
A1 Weyn-Vanhentenryck, Sebastien M.
A1 Feng, Huijuan
A1 Ustianenko, Dmytro
A1 Duffié, Rachel
A1 Yan, Qinghong
A1 Jacko, Martin
A1 Martinez, Jose C.
A1 Goodwin, Marianne
A1 Zhang, Xuegong
A1 Hengst, Ulrich
A1 Lomvardas, Stavros
A1 Swanson, Maurice S.
A1 Zhang, Chaolin
YR 2018
UL http://biorxiv.org/content/early/2018/01/14/247601.abstract
AB Alternative splicing (AS) is a crucial step of gene expression that must be tightly controlled, but the precise timing of dynamic splicing switches during neural development and the underlying regulatory mechanisms are poorly understood. Here we systematically analyzed the temporal regulation of AS in a large number of transcriptome profiles of developing mouse cortices, in vivo purified neuronal subtypes, and neurons differentiated in vitro. Our analysis revealed early- and late-switch exons in genes with distinct functions, and these switches accurately define neuronal maturation stages. Integrative modeling suggests that these switches are under direct and combinatorial regulation by distinct sets of neuronal RNA-binding proteins including Nova, Rbfox, Mbnl and Ptbp. Surprisingly, various neuronal subtypes in the sensory systems lack Nova and/or Rbfox expression. These neurons retain the “immature” splicing program in early-switch exons, affecting numerous synaptic genes. These results provide new insights into the organization and regulation of the neurodevelopmental transcriptome.