Vela Elena, Roca Xavier, Isamat Marcos
Fundación Echevarne, Barcelona, Spain.
Biochem Biophys Res Commun. 2006 Apr 28;343(1):167-70. doi: 10.1016/j.bbrc.2006.02.128. Epub 2006 Mar 2.
The CD44 gene contains 10 variable exons (v1-v10) that can be alternatively spliced to generate hundreds of different CD44 protein isoforms, several of which have been implicated in the metastatic spread of tumour cells. Here, we describe a cryptic splice site, in intron 6 of the human CD44 gene, used during mRNA processing. This cryptic splice site is used in conjunction with variable exon 3, or independently from it in the form of a pseudo-exon of 49 bp, which generates a stop codon by frame shift in the contiguous variable exon downstream. This pseudo-exon has been found inserted immediately 3' to any other variable exon from v4 to v10, in the final CD44 mRNA. The implication of this cryptic splice site in haltering CD44 protein translation is questioned in the context of Nonsense Mediated Decay and the overall regulation of CD44 expression.
CD44基因包含10个可变外显子(v1 - v10),这些外显子可进行可变剪接,从而产生数百种不同的CD44蛋白异构体,其中几种与肿瘤细胞的转移扩散有关。在此,我们描述了人类CD44基因内含子6中一个在mRNA加工过程中使用的隐蔽剪接位点。这个隐蔽剪接位点与可变外显子3一起使用,或以49 bp的假外显子形式独立于可变外显子3使用,它通过下游相邻可变外显子中的移码产生一个终止密码子。在最终的CD44 mRNA中,已发现这个假外显子紧接在从v4到v10的任何其他可变外显子的3'端插入。在无义介导的衰变和CD44表达的整体调控背景下,这个隐蔽剪接位点在阻止CD44蛋白翻译中的作用受到质疑。