Functional coordination of alternative splicing in the mammalian central nervous system

Abstract

Alternative splicing in the central nervous system <p>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.</p> Abstract Background: Alternative splicing (AS) functions to expand proteomic complexity and plays numerous important roles in gene regulation. However, the extent to which AS coordinates functions in a cell and tissue type specific manner is not known. Moreover, the sequence code that underlies cell and tissue type specific regulation of AS is poorly understood.

A postnatal switch of CELF and MBNL proteins reprograms alternative splicing in the developing heart

“…These results demonstrate that during heart development, distinct subsets of genes are regulated by changes in splicing and by changes in transcript levels. Similar results have been demonstrated in comparisons of splicing and mRNA profiles in adult tissues and during T cell activation (11,13,15,19).…”

“…CELF and MBNL proteins were first characterized as factors involved in the pathogenesis of myotonic dystrophy and were subsequently shown to be direct regulators of AS (6)(7)(8). Recent advances in microarray and computational technologies have allowed comprehensive analyses of individual exons on a genome-wide scale, providing the ability to identify commonly regulated splicing events (9)(10)(11)(12).…”

“…With some exceptions (13,14), most large-scale analyses of regulated splicing have focused primarily on differences between adult tissues and tissues/cell cultures depleted for a splicing regulator rather than normal physiological transitions within a single tissue (9)(10)(11)15). Developmental transitions provide an excellent opportunity to identify and determine the roles for coordinated splicing regulation associated with normal physiological change.…”

“…CELF and MBNL proteins were first characterized as factors involved in the pathogenesis of myotonic dystrophy and were subsequently shown to be direct regulators of AS (6-8). Recent advances in microarray and computational technologies have allowed comprehensive analyses of individual exons on a genome-wide scale, providing the ability to identify commonly regulated splicing events (9-12).With some exceptions (13,14), most large-scale analyses of regulated splicing have focused primarily on differences between adult tissues and tissues/cell cultures depleted for a splicing regulator rather than normal physiological transitions within a single tissue (9)(10)(11)15). Developmental transitions provide an excellent opportunity to identify and determine the roles for coordinated splicing regulation associated with normal physiological change.…”

Global analysis of mRNA splicing

“…Thus, most versions of these arrays include probes within constitutive exons so that transcripts can first be scored as present or absent from the sample, then assessed for AS based on junction probes. Splice junction arrays have proven valuable in functional classification of RNA processing mutants in yeast (Clark et al 2002;Burckin et al 2005) and definition of tissuespecific splicing patterns and regulatory motifs in mammalian cells (Johnson et al 2003;Pan et al 2004;Sugnet et al 2006;Fagnani et al 2007). The latter studies have produced the recurring observation that transcripts regulated at the level of alternative splicing comprise a distinct population from those regulated at the level of transcript abundance.…”