Contemporary retrotransposition of a novel non-coding gene induces exon-skipping in dystrophin mRNA
Contemporary retrotransposition of a novel non-coding gene induces exon-skipping in dystrophin mRNA
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DOI：
10.1038/jhg.2010.111
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发表时间：
2010-12-01
影响因子：
3.5
通讯作者：
Matsuo, Masafumi
中科院分区：
文献类型：
--
作者：
Awano, Hiroyuki;Malueka, Rusdy Ghazali;Matsuo, Masafumi
Alu家族的非自主反转录转座子介导的动员是已知的人类疾病的致病机制。在这里，我们报告了一种致病的、当代的、非自主的将部分新的非编码基因反转录转移到Dstrophin基因的方法。在一例日本Duchenne肌营养不良症患者中，在dystrophin的外显子67上发现了一个330个碱基的从头插入。该插入诱导了dystrophin基因外显子67的跳跃，产生了一个提前终止密码子。该插入序列具有逆转录转座子的某些特征：反义多聚腺苷酸化信号伴随多聚(T)序列和靶点重复。尽管插入的序列与任何已知的逆转座子都不匹配，但插入的序列与L1内切酶的共识识别序列相匹配，表明存在逆转录转座子介导的事件。插入序列的起始点被定位在11号染色体的基因缺失区域。插入的片段在多个人类组织RNA中表达，表明它是一个新的转录本。该转录本的全长被克隆，没有显示有意义的蛋白质编码能力。《人类遗传学杂志》(2010年)55785-790DOI：10.1038/jhg.2010.111；2010年9月9日在线出版
Non-autonomous retrotransposon-mediated mobilizations of the Alu family are known pathogenic mechanisms of human disease. Here, we report a pathogenic, contemporary, non-autonomous retrotransmobilization of part of a novel non-coding gene into the dystrophin gene. In a Japanese Duchenne muscular dystrophy patient, a 330-bp-long de novo insertion was identified in exon 67 of dystrophin. The insertion induced exon 67-skipping in the dystrophin mRNA, creating a premature stop codon. The sequence of the insertion had certain characteristics of retrotransposons: an antisense polyadenylation signal accompanied by a poly(T) sequence and a target site duplication. The insertion site matched the consensus recognition sequence for the L1 endonuclease, indicating a retrotransposon-mediated event, although the inserted sequence did not match any known retrotransposons. The origin of the inserted sequence was mapped to a gene-poor region of chromosome 11. The inserted fragment was expressed in multiple human tissue RNAs, indicating that it is a novel transcript. The full length of the transcript was cloned and showed no meaningful protein coding ability. Journal of Human Genetics (2010) 55, 785-790; doi:10.1038/jhg.2010.111; published online 9 September 2010