A family of human microRNA genes from miniature inverted-repeat transposable elements.

A family of human microRNA genes from miniature inverted-repeat transposable elements.
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来自微型倒重复转座元件的人类microRNA基因家族。

DOI:
10.1371/journal.pone.0000203
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发表时间:
2007-02-14
期刊:
影响因子:
3.7
通讯作者:
Jordan, I. King
Jordan, I. King
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Piriyapongsa, Jittima;Jordan, I. King

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虽然仅在过去几年中就发现了数百种新的microRNA(miRNA)基因,但这些非编码调控序列的起源和进化仍然很不清楚。在这份报告中,我们证明了最近发现的人类miRNA基因家族hsa-mir-548的成员来自Made 1转座因子。Made 1元件是由两个37 bp的末端反向重复序列组成的短小的微型反向重复转座元件(MITEs),位于6 bp的内部序列两侧。因此,Made 1元件几乎是完美的回文序列,当表达为RNA时,它们形成高度稳定的发夹环。显然,这些Made 1相关的结构被RNA干扰酶机制识别,并被加工形成22 bp的成熟miRNA序列。hsa-mir-548基因是灵长类动物特异性的,在人类基因组中有许多潜在的旁系同源物,这与它们起源于MITE一致。有超过3,500个假定的hsa-mir-548靶基因;对它们的表达谱和功能亲和力的分析表明hsa-mir-548具有与癌症相关的调节作用。总的来说,Made 1元件和MITE的特征指向了在整个基因组中产生许多小调控RNA和靶位点的特定机制。MITE的进化谱系特异性也可以提供与物种多样化相关的新的监管表型的产生。最后,我们提出,MITE可能代表了siRNA和miRNA之间的进化联系。
While hundreds of novel microRNA (miRNA) genes have been discovered in the last few years alone, the origin and evolution of these non-coding regulatory sequences remain largely obscure. In this report, we demonstrate that members of a recently discovered family of human miRNA genes, hsa-mir-548, are derived from Made1 transposable elements. Made1 elements are short miniature inverted-repeat transposable elements (MITEs), which consist of two 37 base pair (bp) terminal inverted repeats that flank 6 bp of internal sequence. Thus, Made1 elements are nearly perfect palindromes, and when expressed as RNA they form highly stable hairpin loops. Apparently, these Made1-related structures are recognized by the RNA interference enzymatic machinery and processed to form 22 bp mature miRNA sequences. Consistent with their origin from MITEs, hsa-mir-548 genes are primate-specific and have many potential paralogs in the human genome. There are more than 3,500 putative hsa-mir-548 target genes; analysis of their expression profiles and functional affinities suggests cancer-related regulatory roles for hsa-mir-548. Taken together, the characteristics of Made1 elements, and MITEs in general, point to a specific mechanism for the generation of numerous small regulatory RNAs and target sites throughout the genome. The evolutionary lineage-specific nature of MITEs could also provide for the generation of novel regulatory phenotypes related to species diversification. Finally, we propose that MITEs may represent an evolutionary link between siRNAs and miRNAs.
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