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首页> 外文期刊>Journal of Molecular Biology >Exonization of Alu-generated splice variants in the survivin gene of human and non-human primates.
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Exonization of Alu-generated splice variants in the survivin gene of human and non-human primates.

机译：人和非人灵长类动物的survivin基因中Alu产生的剪接变体的外显子化。

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Survivin is a member of the inhibitor apoptosis family that is overexpressed in many malignancies. It has five known alternative splice forms, some of which differ in their antiapoptotic properties and expression levels in human cancers. Here we describe a novel donor splice site (DSS), 2B+32 DSS, which is used in conjunction with survivin alternative exon 2B, resulting in the inclusion of 32 additional nucleotides from intron 2 at the 3' end of this exon. Sequence analysis showed that both the classical exon 2B DSS and 2B+32 are provided by an Alu sequence, which is inserted in intron 2 downstream of a functional acceptor splice site, leading to the exonization of part of the repetitive element. Minor transcripts including the 2B+32 alternative exon, or retaining the whole intronic region comprised between exons 2B and 3, were detected in several human cell lines and in some human tissues. Survivin 2B+32 containing variants acquire a premature stop codon (PTC) and may therefore be degraded by the nonsense mediated decay pathway. The implication of these novel isoforms, as well as other PTC+ survivin variants, in the overall regulation of survivin expression is discussed. Sequence analysis of intron 2 which contains the Alu Y element was performed on different primate species in order to trace its insertion and exonization during primate evolution.
机译：存活蛋白是在许多恶性肿瘤中过表达的抑制剂凋亡家族的成员。它具有五种已知的替代剪接形式，其中一些在人类癌症中的抗凋亡特性和表达水平不同。在这里，我们描述了一个新的供体剪接位点（DSS），2B + 32 DSS，它与survivin替代外显子2B结合使用，导致在该外显子的3'端包含来自内含子2的32个其他核苷酸。序列分析表明，经典的外显子2B DSS和2B + 32均由Alu序列提供，该序列插入到功能性受体剪接位点下游的内含子2中，导致部分重复元件外显子化。在几个人类细胞系和某些人类组织中检测到包括2B + 32替代外显子或保留外显子2B和3之间的整个内含子区域的次要转录物。包含Survivin 2B + 32的变体会获得一个提前终止密码子（PTC），因此可能会被无意义的介导的衰变途径降解。讨论了这些新的同工型以及其他PTC + survivin变体在survivin表达的总体调控中的意义。为了在灵长类动物进化过程中追踪其插入和外显子化，对不同的灵长类动物进行了包含Alu Y元件的内含子2的序列分析。

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