A new role for expressed pseudogenes as ncRNA: regulation of mRNA stability of its homologous coding gene
A new role for expressed pseudogenes as ncRNA: regulation of mRNA stability of its homologous coding gene
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DOI：
10.1007/s00109-004-0550-3
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发表时间：
2004-05
期刊：
影响因子：
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通讯作者：
Y. Yano;R. Saito;Noriyuki Yoshida;A. Yoshiki;A. Wynshaw-Boris;M. Tomita;S. Hirotsune
中科院分区：
文献类型：
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作者：
Y. Yano;R. Saito;Noriyuki Yoshida;A. Yoshiki;A. Wynshaw-Boris;M. Tomita;S. Hirotsune
我们先前在制作转基因品系的过程中产生了一只突变小鼠，该小鼠表现出有趣的杂合子表型，表现出无法茁壮成长、严重的骨畸形和多囊性肾。这种突变小鼠为揭示表达假基因的独特作用提供了线索。在该突变体中，转基因被整合到Makorin 1的表达假基因Makorin 1-p1附近，该插入通过Makorin 1和Makorin 1-p1之间同源的Makorin 1 5′区域内的酸作用RNA衰变元件减少了Makorin 1-p1的转录，导致Makorin 1 mRNA的反式不稳定。这些发现证明了一个新的和特定的表达假基因的调节作用，以及非编码RNA的功能意义。接下来，我们开发了一个原始算法来确定有多少假基因被表达。根据我们的研究，2-3%的人类加工假基因使用最严格的标准表达。有趣的是，小鼠表达的假基因比例要小得多（0.5-1%）。假基因在功能上受限制较少，并且比翻译基因积累了更多的突变。如果它们在基因调节中具有一些功能，那么这种特性将比蛋白质编码基因更快地实现功能多样化。此外，一些表现出不完全遗传的遗传现象可能归因于假基因的“突变”或“变异”。
We have earlier generated a mutant mouse in a course of making a transgenic line that exhibited interesting heterozygote phenotypes, which exhibited failure to thrive, severe bone deformities, and polycystic kidneys. This mutant mouse provided a clue to uncover a unique role of expressed pseudogenes. In this mutant the transgene was integrated into the vicinity of the expressing pseudogene ofMakorin1calledMakorin1-p1.This insertion reduced transcription of theMakorin1-p1, resulting in destabilization of theMakorin1mRNA in trans via acis-acting RNA decay element within the 5′ region ofMakorin1that is homologous betweenMakorin1andMakorin1-p1. These findings demonstrate a novel and specific regulatory role of an expressed pseudogene as well as functional significance for noncoding RNAs. Next, we developed an original algorithm to determine how many pseudogenes are expressed. Based on our examination 2–3% of human processed pseudogenes are expressed using the most strict criteria. Interestingly, the mouse has a much smaller proportion of expressed pseudogenes (0.5–1%). Pseudogenes are functionally less constrained, and have accumulated more mutations than translated genes. If they have some functions in gene regulation, this property would allow more rapid functional diversification than protein-coding genes. In addition, some genetic phenomena that exhibit incomplete penetrance might be attributed to “mutation” or “variation” of pseudogenes.