Evolutionary conservation and tissue-specific processing of Hoxa 11 antisense transcripts
Evolutionary conservation and tissue-specific processing of Hoxa 11 antisense transcripts
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DOI：
10.1007/s003359900870
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发表时间：
1998-10-01
期刊：
影响因子：
2.5
通讯作者：
Branford, WW
中科院分区：
文献类型：
--
作者：
Potter, SS;Branford, WW
我们先前描述了存在丰富的，加工，多腺苷酸化的小鼠Hoxa 11反义转录。特别令人感兴趣的是，在发育中的肢体中，观察到反义转录物以与有义转录物互补的模式存在，表明可能的调节功能（Hsieh-Li et al. 1995）。我们已经分析了人类HOXA 11基因组位点，显示出潜在编码反义转录物的区域的强进化保守性。鉴定并测序了人HOXA 11胎肾反义cDNA，证明了Hoxa 11反义转录的进化保守性。对于小鼠，人反义RNA被聚腺苷酸化，并显示出几种可选的加工模式，但共享一个共同的3'外显子序列。相反链转录本的进化保守性强烈表明了功能。一个显着长的开放阅读框架进行了观察，但小鼠和人类的比较反对真正的编码功能。还检查了小鼠肾脏Hoxa 11反义转录和加工，揭示了肢体和肾脏之间的组织特异性差异。一种新的程序，指定种族的圆圈，被设计和用于定义小鼠肢体反义转录起始位点。此外，人类，小鼠和鸡的正义转录Hoxa 11同源框核苷酸序列和它们各自编码的同源结构域的比较表明，在脊椎动物中对导致编码变化的突变有非常强的选择压力。鉴于不同Hox基因同源结构域的氨基酸序列存在显著差异，这一观察结果支持个体同源结构域功能特异性。
We previously described the existence of abundant, processed, polyadenylated murine Hoxa 11 antisense transcripts. Of particular interest, in the developing limbs the antisense transcripts were observed to be present in a pattern complementary to that of the sense transcripts, suggesting a possible regulatory function (Hsieh-Li et al. 1995). We have analyzed the human HOXA 11 genomic locus, showing strong evolutionary conservation of regions potentially encoding antisense transcripts. Human HOXA 11 fetal kidney antisense cDNAs were identified and sequenced, demonstrating the evolutionary conservation of Hoxa 11 antisense transcription. As for the mouse, the human antisense RNAs were polyadenylated and showed several alternative processing patterns, but shared the sequences of a common 3' exon. The evolutionary conservation of the opposite strand transcripts strongly suggests function. A significantly long open reading frame was observed, but mouse-human comparisons argued against true coding function. Murine kidney Hoxa 11 antisense transcription and processing was also examined, revealing tissue-specific differences between limb and kidney. A novel procedure, designated Race in Circles, was devised and used to define mouse limb antisense transcription start sites. Furthermore, comparisons of human, mouse, and chicken sense transcript Hoxa 11 homeobox nucleotide sequences and their respective encoded homeodomains indicate a very strong selective pressure in vertebrates against mutations that result in coding changes. Given the significant differences in amino acid sequences of the homeodomains of different Hox genes, this observation argues for individual homeodomain functional specificity.