Cryptic splice site usage in exon 7 of the human fibrinogen Bbeta-chain gene is regulated by a naturally silent SF2/ASF binding site within this exon.
Cryptic splice site usage in exon 7 of the human fibrinogen Bbeta-chain gene is regulated by a naturally silent SF2/ASF binding site within this exon.
复制标题
人纤维蛋白原 Bβ 链基因外显子 7 中隐秘剪接位点的使用受到该外显子内天然沉默的 SF2/ASF 结合位点的调节。
作者：
S. Spena;M. Tenchini;E. Buratti
在这项工作中，我们报告了一个强大的SF 2/ASF结合位点内的人纤维蛋白原B β链基因（FGB）的外显子7的鉴定。其在野生型环境中的破坏对外显子识别没有影响。然而，当存在突变IVS 7 + 1G>T（最初在患有先天性无纤维蛋白原血症的患者中描述）时，该SF 2/ASF结合位点对于神秘的5 'ss（剪接位点）定义至关重要。这些发现，除了确认和扩展以前的结果SF 2/ASF对隐蔽剪接位点激活的影响，确定了第一次在FGB基因特异性的隐蔽剪接位点使用的增强子序列。两者合计，他们建议存在一个剪接调控网络，通常是沉默的FGB自然剪接环境，但仍然可以影响剪接的决定时，当地的情况允许。在一个更普遍的注意，我们的结论有影响的选择性剪接过程的演变和发展的方法来控制异常剪接的背景下，致病突变。
In this work we report the identification of a strong SF2/ASF binding site within exon 7 of the human fibrinogen Bbeta-chain gene (FGB). Its disruption in the wild-type context has no effect on exon recognition. However, when the mutation IVS7 + 1G>T--initially described in a patient suffering from congenital afibrinogenemia--is present, this SF2/ASF binding site is critical for cryptic 5'ss (splice site) definition. These findings, besides confirming and extending previous results regarding the effect of SF2/ASF on cryptic splice site activation, identify for the first time an enhancer sequence in the FGB gene specific for cryptic splice site usage. Taken together, they suggest the existence of a splicing-regulatory network that is normally silent in the FGB natural splicing environment but which can nonetheless influence splicing decisions when local contexts allow. On a more general note, our conclusions have implications for the evolution of alternative splicing processes and for the development of methods to control aberrant splicing in the context of disease-causing mutations.