A potential role for RNA interference in controlling the activity of the human LINE-1 retrotransposon

被引:75
|
作者
Soifer, HS
Zaragoza, A
Peyvan, M
Behlke, MA
Rossi, JJ
机构
[1] City Hope Natl Med Ctr, Div Mol Biol, Duarte, CA 91010 USA
[2] City Hope Natl Med Ctr, Grad Sch Biol Sci, Beckman Res Inst, Duarte, CA 91010 USA
[3] Integrated DNA Technol Inc, Div Mol Genet, Coralville, IA 53341 USA
关键词
D O I
10.1093/nar/gki223
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Long interspersed nuclear elements (LINE-1 or L1) comprise 17% of the human genome, although only 80-100 L1s are considered retrotransposition-competent (RC-L1). Despite their small number, RC-L1s are still potential hazards to genome integrity through insertional mutagenesis, unequal recombination and chromosome rearrangements. In this study, we provide several lines of evidence that the LINE-1 retrotransposon is susceptible to RNA interference (RNAi). First, double-stranded RNA (dsRNA) generated in vitro from an L1 template is converted into functional short interfering RNA (siRNA) by DICER, the RNase III enzyme that initiates RNAi in human cells. Second, pooled siRNA from in vitro cleavage of L1 dsRNA, as well as synthetic L1 siRNA, targeting the 5'-UTR leads to sequence-specific mRNA degradation of an L1 fusion transcript. Finally, both synthetic and pooled siRNA suppressed retrotransposition from a highly active RC-L1 clone in cell culture assay. Our report is the first to demonstrate that a human transposable element is subjected to RNAi.
引用
收藏
页码:846 / 856
页数:11
相关论文
共 50 条
  • [41] Pathogenic Orphan Transduction Created by a Nonreference LINE-1 Retrotransposon
    Solyom, Szilvia
    Ewing, Adam D.
    Hancks, Dustin C.
    Takeshima, Yasuhiro
    Awano, Hiroyuki
    Matsuo, Masafumi
    Kazazian, Haig H., Jr.
    HUMAN MUTATION, 2012, 33 (02) : 369 - 371
  • [42] Epigenetic control of mammalian LINE-1 retrotransposon by retinoblastoma proteins
    Montoya-Durango, Diego E.
    Liu, Yongqing
    Teneng, Ivo
    Kalbfleisch, Ted
    Lacy, Mary E.
    Steffen, Marlene C.
    Ramos, Kenneth S.
    MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 2009, 665 (1-2) : 20 - 28
  • [43] Generation of cytoplasmic DNA of an RNA virus by human LINE-1
    Shimizu, Akira
    Nakatani, Yoko
    Nakamura, Takako
    Ishikawa, Osamu
    Takeuchi, Yasuhiro
    Hoshino, Hiroo
    JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2010, 130 : S93 - S93
  • [44] Nucleic acid chaperone activity of the ORF1 protein from the mouse LINE-1 retrotransposon
    Martin, SL
    Bushman, FD
    MOLECULAR AND CELLULAR BIOLOGY, 2001, 21 (02) : 467 - 475
  • [45] Sense transcripts originated from an internal part of the human retrotransposon LINE-1 5′ UTR
    Alexandrova, Elena A.
    Olovnikov, Ivan A.
    Malakhova, Galina V.
    Zabolotneva, Anastasia A.
    Suntsova, Maria V.
    Dmitriev, Sergey E.
    Buzdin, Anton A.
    GENE, 2012, 511 (01) : 46 - 53
  • [46] RNA sensor MDA5 suppresses LINE-1 retrotransposition by regulating the promoter activity of LINE-1 5′-UTR
    Yan, Jiaxiu
    Zhao, Yifei
    Du, Juan
    Wang, Yu
    Wang, Shaohua
    Wang, Qing
    Zhao, Xu
    Xu, Wei
    Zhao, Ke
    MOBILE DNA, 2022, 13 (01)
  • [47] RNA sensor MDA5 suppresses LINE-1 retrotransposition by regulating the promoter activity of LINE-1 5′-UTR
    Jiaxiu Yan
    Yifei Zhao
    Juan Du
    Yu Wang
    Shaohua Wang
    Qing Wang
    Xu Zhao
    Wei Xu
    Ke Zhao
    Mobile DNA, 13
  • [48] DNA release by line-1 (L1) retrotransposon - Could it be possible?
    Alves, G
    Kawamura, MT
    Nascimento, P
    Maciel, C
    Oliveira, JA
    Teixeira, A
    Carvalho, MDC
    CIRCULATING NUCLEIC ACIDS IN PLASMA OR SERUM, 2000, 906 : 129 - 133
  • [49] LINE-1 RETROTRANSPOSON EXPRESSION IN PEDIATRIC GERM-CELL TUMORS
    BRATTHAUER, GL
    FANNING, TG
    CANCER, 1993, 71 (07) : 2383 - 2386
  • [50] Superovulation induces defective methylation in line-1 retrotransposon elements in blastocyst
    Xing-Wei Liang
    Xiang-Shun Cui
    Shao-Chen Sun
    Yong-Xun Jin
    Young Tae Heo
    Suk Namgoong
    Nam-Hyung Kim
    Reproductive Biology and Endocrinology, 11