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完整内含子序列的微小RNA样效应。

Micro-RNA-like effects of complete intronic sequences.

作者信息

Hill Aubrey E, Hong Jeong S, Wen Hui, Teng LiHong, McPherson David T, McPherson Sylvia A, Levasseur Dana N, Sorscher Eric J

机构信息

Pittman General Clinical Research Center, University of Alabama, Birmingham, Alabama 35294, USA.

出版信息

Front Biosci. 2006 May 1;11:1998-2006. doi: 10.2741/1941.

Abstract

MicroRNAs (miRNAs) have been suggested as suppressors of numerous target genes in human cells. In this report, we present gene chip array data indicating that in the absence of miRNA sequences, complete human introns are similarly capable of coordinating expression of large numbers of gene products at spatially diverse sites within the genome. The expression of selected intronic sequences (6a, 14b and 23) derived from the cystic fibrosis transmembrane conductance regulator (CFTR) gene caused extensive and specific transcriptional changes in epithelial cells (HeLa) that do not normally express this gene product. Each intron initiated a distinctive pattern of gene transcription. Affected genes such as FOXF1, sucrase-isomaltase, collagen, interferon, complement and thrombospondin 1 have previously been linked to CFTR function or are known to contribute to the related processes of epithelial differentiation and repair. A possible regulatory function of this nature has not been demonstrated previously for non-coding sequences within eukaryotic DNA. The results are consistent with the observation that splicesomal introns are found only in eukaryotic organisms and that the number of introns increases with phylogenetic complexity.

摘要

微小RNA(miRNAs)被认为是人类细胞中众多靶基因的抑制因子。在本报告中,我们展示了基因芯片阵列数据,表明在没有miRNA序列的情况下,完整的人类内含子同样能够在基因组内空间上不同的位点协调大量基因产物的表达。源自囊性纤维化跨膜传导调节因子(CFTR)基因的选定内含子序列(6a、14b和23)的表达,在通常不表达该基因产物的上皮细胞(HeLa)中引起了广泛而特异性的转录变化。每个内含子引发了独特的基因转录模式。受影响的基因,如FOXF1、蔗糖酶-异麦芽糖酶、胶原蛋白、干扰素、补体和血小板反应蛋白1,先前已与CFTR功能相关联,或者已知它们参与上皮分化和修复的相关过程。这种性质的可能调节功能以前尚未在真核DNA的非编码序列中得到证实。这些结果与以下观察结果一致:剪接体内含子仅在真核生物中发现,并且内含子的数量随着系统发育复杂性的增加而增加。

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