Functional coordination of alternative splicing in the mammalian central nervous system

Matthew Fagnani,Arneet L Saltzman,Ofer Shai,Joanna Y Ip,Naveed Mohammad,Benjamin J Blencowe,Timothy R Hughes,Yoseph Barash,Qun Pan,Sandrine Willaime-Morawek,Leo Lee,Brendan J Frey,Wen Zhang,Derek Van Der Kooy,Tomas Babak,Christine Misquitta,Aviad Rozenhek

doi:10.1186/gb-2007-8-6-r108

Matthew Fagnani, Arneet L Saltzman + Show 15 more

Open Access

https://doi.org/10.1186/gb-2007-8-6-r108

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Abstract

A microarray analysis provides new evidence suggesting that specific cellular processes in the mammalian CNS are coordinated at the level of alternative splicing, and that a complex splicing code underlies CNS-specific alternative splicing regulation.

Highlights

Alternative splicing (AS) functions to expand proteomic complexity and plays numerous important roles in gene regulation
To assess more systematically the functions of the genes containing alternative exons with central nervous system (CNS) associated alternative splicing (AS) levels, and to address whether these genes operate in common cellular processes and pathways, we considered whether genes with the most significant CNS associated AS level differences are enriched in Gene Ontology (GO) terms
Using a new AS microarray applied to the profiling of 27 diverse mouse cell and tissue types, we detected a large number of new examples of tissue dependent differential regulation of AS

Summary

Introduction

Alternative splicing (AS) functions to expand proteomic complexity and plays numerous important roles in gene regulation. The extent to which AS coordinates functions in a cell and tissue type specific manner is not known. Alternative splicing (AS) is the process by which the exon sequences of primary transcripts are differentially included in mature mRNA, and it represents an important mechanism underlying the regulation and diversification of gene function [1,2,3,4]. Comparisons of data from transcript sequencing efforts and microarray profiling experiments have provided evidence that AS is more frequent in organisms with increased cellular and functional specialization [4,5,6]. The extent to which AS events in different cell and tissue types are regulated in a coordinated fashion to control specific cellular functions and processes is not known. Binding of Tra to a specialized exonic splicing enhancer element regulates the AS of transcripts encoding the transcription factors Doublesex and Fruitless, which activate sets of genes that are involved in sex determination and courtship behavior, respectively [11,12]

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