Dysregulated minor intron splicing in cancer.
Dysregulated minor intron splicing in cancer.
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作者：
转录前剪接被广泛认为是一种共转录和转录后机制，对调节基因表达和改变基因产物功能至关重要。编码核心剪接体蛋白和辅助调控剪接因子的基因突变现在被认为是癌症患者，特别是血液系统恶性肿瘤患者最常见的遗传异常之一。这些突变包括主要剪接体(U2型)和次要剪接体(U12型)的突变，它们分别去除了99%和~0.35%的内含子。越来越多的证据表明，进化上保守的U12型微小内含子的异常剪接在癌症中起着至关重要的作用，因为微小剪接体成分ZRSR2容易发生与白血病相关的反复突变，而内含子突变已被证明扰乱了微小内含子的剪接。在这里，我们综述了微小内含子调控的重要性，微小(U12型)剪接体突变和顺式调控区的分子效应，以及为了更好地了解癌症生物学而进行的微小内含子研究的进展。
Pre‐mRNA splicing is now widely recognized as a cotranscriptional and post‐transcriptional mechanism essential for regulating gene expression and modifying gene product function. Mutations in genes encoding core spliceosomal proteins and accessory regulatory splicing factors are now considered among the most recurrent genetic abnormalities in patients with cancer, particularly hematologic malignancies. These include mutations in the major (U2‐type) and minor (U12‐type) spliceosomes, which remove >99% and ~0.35% of introns, respectively. Growing evidence indicates that aberrant splicing of evolutionarily conserved U12‐type minor introns plays a crucial role in cancer as the minor spliceosome component, ZRSR2, is subject to recurrent, leukemia‐associated mutations, and intronic mutations have been shown to disrupt the splicing of minor introns. Here, we review the importance of minor intron regulation, the molecular effects of the minor (U12‐type) spliceosomal mutations and cis‐regulatory regions, and the development of minor intron studies for better understanding of cancer biology.
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影响因子：
11.4
作者：
通讯作者：
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与U2内含子位置相比，在动物和植物之间，U12内含子位置更为强烈。
影响因子：
5.5
作者：
Basu, Malay Kumar;Makalowski, Wojciech;Rogozin, Igor B.;Koonin, Eugene V.
通讯作者：
Koonin, Eugene V.
影响因子：
30.8
作者：
Harbour, J. William;Roberson, Elisha D. O.;Anbunathan, Hima;Onken, Michael D.;Worley, Lori A.;Bowcock, Anne M.
通讯作者：
Bowcock, Anne M.
影响因子：
56.9
作者：
Castel, Pau;Cheng, Alice;McCormick, Frank
通讯作者：
McCormick, Frank
影响因子：
8.8
作者：
Darman, Rachel B.;Seiler, Michael;Buonamici, Silvia
通讯作者：
Buonamici, Silvia