Stepwise assembly of the Nova -regulated alternative splicing network in the vertebrate brain

• DOI: 10.1073/pnas.1012333108
• Publication Date: 2011-03-10T04:12:59Z
• Authors: Manuel Irimia; Amanda Denuc; Demián Burguera; Ildiko Somorjai; Jose M. Martín-Durán; Grigory Genikhovich; Senda Jimenez-Del...; Ulrich Technau; Scott W. Roy; Gemma Marfany; Jordi Garcia-Fern...
• Keywords: Chordate

Novel organismal structures in metazoans are often undergirded by complex gene regulatory networks; as such, understanding the emergence of new through evolution requires reconstructing series evolutionary steps leading to these underlying networks. Here, we reconstruct step-by-step assembly vertebrate splicing network regulated Nova , a factor that modulates alternative central nervous system binding clusters YCAY motifs on pre-RNA transcripts. Transfection human HEK293T cells with orthologs indicated vertebrate-like activity bilaterian invertebrates, thus acquired ability bind and perform modulation at least before last common ancestor bilaterians. In situ hybridization studies several species showed expression became restricted CNS later on, during chordate evolution. Finally, comparative genomics revealed diverse history for -regulated exons, target exons arising both de novo exon creation acquisition preexisting throughout history. addition, find tissue-specific patterns emerged independently other lineages, suggesting independent