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LINE插入序列5'连接产生的整合机制。

Integrated mechanism for the generation of the 5' junctions of LINE inserts.

作者信息

Yamaguchi Katsumi, Kajikawa Masaki, Okada Norihiro

机构信息

Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259-B-15 Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa 226-8501, Japan.

Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259-B-15 Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa 226-8501, Japan

出版信息

Nucleic Acids Res. 2014 Dec 1;42(21):13269-79. doi: 10.1093/nar/gku1067. Epub 2014 Nov 6.

DOI:10.1093/nar/gku1067
PMID:25378331
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4245944/
Abstract

To elucidate the molecular mechanism of the integration of long interspersed elements (LINEs), we characterized the 5' ends of more than 200 LINE de novo retrotransposition events into chicken DT40 or human HeLa cells. Human L1 inserts produced 15-bp target-site duplications (TSDs) and zebrafish ZfL2-1 inserts produced 5-bp TSDs in DT40 cells, suggesting that TSD length depends on the LINE species. Further analysis of 5' junctions revealed that the 5'-end-joining pathways of LINEs can be divided into two fundamental types-annealing or direct. We also found that the generation of 5' inversions depends on host and LINE species. These results led us to propose a new model for 5'-end joining, the type of which is determined by the extent of exposure of 3' overhangs generated after the second-strand cleavage and by the involvement of host factors.

摘要

为阐明长散在元件（LINEs）整合的分子机制，我们对200多个LINEs从头逆转录转座事件插入鸡DT40细胞或人HeLa细胞的5'端进行了表征。人L1插入在DT40细胞中产生了15 bp的靶位点重复序列（TSDs），斑马鱼ZfL2 - 1插入产生了5 bp的TSDs，这表明TSD长度取决于LINEs种类。对5'连接的进一步分析表明，LINEs的5'末端连接途径可分为两种基本类型——退火型或直接型。我们还发现5'倒位的产生取决于宿主和LINEs种类。这些结果使我们提出了一种新的5'末端连接模型，其类型由第二条链切割后产生的3'突出端的暴露程度以及宿主因子的参与情况决定。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98f7/4245944/ef943d1c6681/gku1067fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98f7/4245944/98e3f332904f/gku1067fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98f7/4245944/afd18121a0dc/gku1067fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98f7/4245944/895787d833ee/gku1067fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98f7/4245944/794f662f3839/gku1067fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98f7/4245944/8daeed1bbbde/gku1067fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98f7/4245944/ef943d1c6681/gku1067fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98f7/4245944/98e3f332904f/gku1067fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98f7/4245944/afd18121a0dc/gku1067fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98f7/4245944/895787d833ee/gku1067fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98f7/4245944/794f662f3839/gku1067fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98f7/4245944/8daeed1bbbde/gku1067fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98f7/4245944/ef943d1c6681/gku1067fig6.jpg

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本文引用的文献

1
A new mechanism to ensure integration during LINE retrotransposition: a suggestion from analyses of the 5' extra nucleotides.一种确保 LINE 逆转录转座过程中整合的新机制：来自 5' 额外核苷酸分析的建议。
Gene. 2012 Sep 1;505(2):345-51. doi: 10.1016/j.gene.2012.02.047. Epub 2012 Mar 1.
2
Ataxia telangiectasia mutated (ATM) modulates long interspersed element-1 (L1) retrotransposition in human neural stem cells.共济失调毛细血管扩张突变基因 (ATM) 调节人类神经干细胞中的长散布元件-1 (L1) 反转录转座。
Proc Natl Acad Sci U S A. 2011 Dec 20;108(51):20382-7. doi: 10.1073/pnas.1100273108. Epub 2011 Dec 9.
3
Self-interaction, nucleic acid binding, and nucleic acid chaperone activities are unexpectedly retained in the unique ORF1p of zebrafish LINE.
在独特的斑马鱼 LINE 的 ORF1p 中出人意料地保留了自我相互作用、核酸结合和核酸伴侣活性。
Mol Cell Biol. 2012 Jan;32(2):458-69. doi: 10.1128/MCB.06162-11. Epub 2011 Nov 21.
4
Nucleic acid chaperone properties of ORF1p from the non-LTR retrotransposon, LINE-1.非长末端重复序列转座子 LINE-1 的 ORF1p 的核酸伴侣特性。
RNA Biol. 2010 Nov-Dec;7(6):706-11. doi: 10.4161/rna.7.6.13766. Epub 2010 Nov 1.
5
Different integration site structures between L1 protein-mediated retrotransposition in cis and retrotransposition in trans.L1 蛋白介导的顺式和反式逆转录转座之间不同的整合位点结构。
Mob DNA. 2010 Jul 8;1(1):17. doi: 10.1186/1759-8753-1-17.
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LINE-1 retrotransposition activity in human genomes.LINE-1 逆转座子在人类基因组中的活性。
Cell. 2010 Jun 25;141(7):1159-70. doi: 10.1016/j.cell.2010.05.021.
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Simple and fast classification of non-LTR retrotransposons based on phylogeny of their RT domain protein sequences.基于非长末端重复反转录转座子反转录酶结构域蛋白质序列系统发育的简单快速分类
Gene. 2009 Dec 15;448(2):207-13. doi: 10.1016/j.gene.2009.07.019. Epub 2009 Aug 3.
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