Cold shock induces the insertion of a cryptic exon in the neurofibromatosis type 1 (NF1) mRNA

Alternative splicing is a regulatory process of gene expression based on th e flexibility in the selection of splice sites. In this manuscript we prese nt the characterisation of an alternative splicing of the NF1 pre-mRNA indu ced by cold-shock conditions. We demonstrate that the accuracy of the splic ing mechanism was perturbed after keeping samples for a short period of tim e at room temperature, resulting in the insertion of a 31-bp cryptic exon b etween exons 4a and 4b of the NF1 mRNA. This alternative splicing is not ce ll type specific and is not induced by other stress conditions such as heat shock or hyperosmolarity. The alternative spliced mRNA is efficiently tran sported to the cytoplasm and it is proven to belong to the poly A(+) mRNA f raction. Previous misleading interpretations about this transcript, togethe r with our finding relating its presence to cold shock and not to the NF1 d isease, strongly indicate that this phenomenon should be taken into account in genetic testing when RNA methodology is used for mutation detection. Th is is the first description of an alternative splicing induced by cold shoc k in a human pre-mRNA and should provide further insights into the factors that control alternative splicing.