Somatic expression of LINE-1 elements in human tissues.
Somatic expression of LINE-1 elements in human tissues.
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DOI：
10.1093/nar/gkq132
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发表时间：
2010-07
影响因子：
14.9
通讯作者：
Deininger P
中科院分区：
文献类型：
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作者：
Belancio VP;Roy-Engel AM;Pochampally RR;Deininger P
LINE-1表达通过插入和核酸内切酶依赖性DNA双链断裂（DSB）破坏宿主DNA，具有高度毒性和致突变性。LINE-1表达的主要组织被认为是生殖系。我们发现，全长和处理L1转录普遍存在于人体组织和转化细胞，在L1的表达和L1 mRNA加工的显着变化。这是第一次证明RNA加工是L1活性的主要调节因子。许多组织也产生可翻译的剪接转录本（SpORF 2）。Alu逆转录转座试验、COMET试验和53 BP 1焦点染色显示SpORF 2产物可以支持功能性ORF 2蛋白表达，并且可以诱导正常细胞中的DNA损伤。衰老相关的β-半乳糖苷酶表达的测试表明，外源全长L1或SpORF 2 mRNA单独在人成纤维细胞和成体干细胞中的表达触发衰老样表型，这是对DNA损伤的报告反应之一。与先前假设L1表达是种系特异性的相反，暴露于L1相关损伤的组织光谱增加表明L1在体细胞组织中作为内源性诱变剂的作用。这些发现对整个生物体有潜在的影响，表现为癌症和哺乳动物衰老。
LINE-1 expression damages host DNA via insertions and endonuclease-dependent DNA double-strand breaks (DSBs) that are highly toxic and mutagenic. The predominant tissue of LINE-1 expression has been considered to be the germ line. We show that both full-length and processed L1 transcripts are widespread in human somatic tissues and transformed cells, with significant variation in both L1 expression and L1 mRNA processing. This is the first demonstration that RNA processing is a major regulator of L1 activity. Many tissues also produce translatable spliced transcript (SpORF2). An Alu retrotransposition assay, COMET assays and 53BP1 foci staining show that the SpORF2 product can support functional ORF2 protein expression and can induce DNA damage in normal cells. Tests of the senescence-associated β-galactosidase expression suggest that expression of exogenous full-length L1, or the SpORF2 mRNA alone in human fibroblasts and adult stem cells triggers a senescence-like phenotype, which is one of the reported responses to DNA damage. In contrast to previous assumptions that L1 expression is germ line specific, the increased spectrum of tissues exposed to L1-associated damage suggests a role for L1 as an endogenous mutagen in somatic tissues. These findings have potential consequences for the whole organism in the form of cancer and mammalian aging.
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LINE-1 RNA剪接和对哺乳动物基因表达的影响。
影响因子：
14.9
作者：
Belancio, VP;Hedges, DJ;Deininger, P
通讯作者：
Deininger, P
影响因子：
14.9
作者：
Farkash EA;Kao GD;Horman SR;Prak ET
通讯作者：
Prak ET
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
影响因子：
30.8
作者：
Dewannieux, M;Esnault, C;Heidmann, T
通讯作者：
Heidmann, T
影响因子：
64.8
作者：
通讯作者：
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