...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nucleic Acids Research >Biased exon/intron distribution of cryptic and de novo 3' splice sites.
【24h】

Biased exon/intron distribution of cryptic and de novo 3' splice sites.

机译：隐性和从头3'剪接位点的外显子/内含子的偏向分布。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

We compiled sequences of previously published aberrant 3' splice sites (3'ss) that were generated by mutations in human disease genes. Cryptic 3'ss, defined here as those resulting from a mutation of the 3'YAG consensus, were more frequent in exons than in introns. They clustered in approximately 20 nt region adjacent to authentic 3'ss, suggesting that their under-representation in introns is due to a depletion of AG dinucleotides in the polypyrimidine tract (PPT). In contrast, most aberrant 3'ss that were induced by mutations outside the 3'YAG consensus (designated 'de novo') were in introns. The activation of intronic de novo 3'ss was largely due to AG-creating mutations in the PPT. In contrast, exonic de novo 3'ss were more often induced by mutations improving the PPT, branchpoint sequence (BPS) or distant auxiliary signals, rather than by direct AG creation. The Shapiro-Senapathy matrix scores had a good prognostic value for cryptic, but not de novo 3'ss. Finally, AG-creating mutations in the PPT that produced aberrant 3'ss upstream of the predicted BPS in vivo shared a similar 'BPS-new AG' distance. Reduction of this distance and/or the strength of the new AG PPT in splicing reporter pre-mRNAs improved utilization of authentic 3'ss, suggesting that AG-creating mutations that are located closer to the BPS and are preceded by weaker PPT may result in less severe splicing defects.
机译：我们编辑了先前发表的由人类疾病基因突变产生的异常3'剪接位点（3's）的序列。隐性3'在这里定义为3'YAG共有基因突变产生的隐性3，在外显子中比内含子更频繁。它们聚集在与真实3's相邻的大约20 nt区域中，表明它们在内含子中的代表性不足是由于聚嘧啶束（PPT）中AG二核苷酸的消耗所致。相反，大多数由3'YAG共有序列（称为“从头”）以外的突变诱导的异常3's是内含子。内源性从头3的激活很大程度上是由于PPT中AG产生的突变。相比之下，外显子从头3's更经常是由改善PPT，分支点序列（BPS）或远距离辅助信号的突变诱导的，而不是由直接产生AG诱导的。 Shapiro-Senapathy矩阵评分对于隐秘患者具有良好的预后价值，但对于新生3评分则没有。最后，在体内预测的BPS上游产生异常3的PPT中产生AG的突变具有相似的'BPS-new AG'距离。减少这一距离和/或新的AG PPT在剪接报告基因前mRNA时的强度提高了对真实3's的利用，这表明AG产生的突变位于更靠近BPS的位置，而PPT较弱则可能导致不太严重的拼接缺陷。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号