Noncoding Constraint On Dna And Gene Regulation

DNA 和基因调控的非编码约束

• 批准号: 7148035
• 负责人: DAVID J. LIPMAN
• 金额: --
• 依托单位: NATIONAL LIBRARY OF MEDICINE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7148035
• 关键词: alleles; antisense nucleic acid; chemical stability; gene interaction; genetic regulation; genetic translation; intermolecular interaction; messenger RNA; nucleic acid sequence; posttranscriptional RNA processing; posttranslational modifications; species difference

A substantial fraction of vertebrate mRNAs contain long conserved blocks in their untranslated regions as well as long blocks without silent changes in their protein coding regions. These conserved blocks are largely comprised of unique sequence within the genome, leaving us with an important puzzle regarding their function. A large body of experimental data shows that these regions are associated with regulation of mRNA stability. Combining this information with the rapidly accumulating data on endogenous antisense transcripts, we propose that the conserved sequences are the result of a trans-allelic interaction possibly involving duplexes between the transcript of one allele and the counter-transcript of the other allele. The formation of such duplexes may be essential for recognition by post-transcriptional regulatory systems. The conservation may then be explained by selection against the dominant negative effect of allelic divergence.

很大一部分脊椎动物mRNA在其未翻译区域中包含长期保守的块，以及长的块，而没有蛋白质编码区域的无声变化。这些保守的块在很大程度上由基因组中的独特序列组成，这使我们对其功能有一个重要的难题。大量的实验数据表明，这些区域与mRNA稳定性的调节有关。将这些信息与内源性反义转录本的快速积累数据相结合，我们建议保守的序列是跨性相互作用的结果，可能涉及一个等位基因的转录本和另一个等位基因的反转录之间的双链体。这种双链体的形成对于通过转录后调节系统识别可能是必不可少的。然后，可以通过选择对等位基因差异的主要负面影响来解释保护。