RNA binding protein regulated differentiation- dependent alternative splicing

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Alternative splicing is a comon mechanism for the generation of multiple mRNAs with different stabilities, translation efficiencies, or protein coding sequences from a single gene. The selection of an alternative exon is often under the control of cell type-specific or differentiation state-dependent splicing machinery. The efficiency of exon selection is determined by a balance of several determinants, such as splice donor and acceptor site sequences, exon size, enhancer and repressor resided in exons and intron, and relative potentials of competing splice site sequences. Most of the cis-acting regulatory elements characterized up to date involved in a constitutive splicing pathway. In mammalian genes, only a limited number of cis-elements that participate in the alternative splicing has been reported. We found for an intronic cis-acting element located downstrem exon MSDb (muscle-specific domain b) in the NCAM (neural cell adhesion molecule) gene. The cis-element acted as a negative regulator for the selection of exon MSDb in nonmuscle fibroblast but not in myoblasts, that are already destined to differentiate into muscle cells. The suppressive effect of this cis-element on the selection of exon MSDb was released in the process of myogenesis. We searched for trans-acting factor (s) that bind to the cisacting elements, such as splicing factors and regulators.