Raponi Michela, Baralle Diana
Human Genetics Division, University of Southampton, Duthie Building (Mailpoint 808), Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK.
Biochem Soc Trans. 2008 Jun;36(Pt 3):548-50. doi: 10.1042/BST0360548.
Many disease-causing mutations affecting donor splice site recognition are reported in the literature. One of the more frequently observed nucleotide changes causing aberrant splicing are due to mutations in the donor splice site which lower the strength of base pairing with U1 snRNA (small nuclear RNA). However, recent data have highlighted the possibility of a recognition mechanism for weak donor splice sites that are at least partially U1-independent. This is important as most of the donor splice site prediction programs currently in use are based on the U1 snRNA 5'-splice site base pairing and would not pick this up. We review these mechanisms and how an up-to-date donor splice site mutation repertoire indicates the heterogeneity of the molecular mechanism. We suggest that, in clinical molecular genetics, it is important to evaluate sequence variants for aberrant splicing even in those cases where the variant is not thought to alter the U1 snRNA interaction.
文献中报道了许多影响供体剪接位点识别的致病突变。导致异常剪接的较常见核苷酸变化之一是由于供体剪接位点的突变，这降低了与U1小核RNA（small nuclear RNA）碱基配对的强度。然而，最近的数据突出了弱供体剪接位点存在至少部分不依赖于U1的识别机制的可能性。这一点很重要，因为目前使用的大多数供体剪接位点预测程序都是基于U1小核RNA 5'-剪接位点的碱基配对，无法识别这种情况。我们回顾了这些机制，以及最新的供体剪接位点突变库如何表明分子机制的异质性。我们认为，在临床分子遗传学中，即使在那些被认为不会改变U1小核RNA相互作用的情况下，评估序列变异是否导致异常剪接也很重要。
