Human Molecular Genetics Advance Access originally published online on September 23, 2005
Human Molecular Genetics 2005 14(21):3237-3248; doi:10.1093/hmg/ddi354
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Ribonucleoprotein particle formation is necessary but not sufficient for LINE-1 retrotransposition
1Department of Human Genetics and 2Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109-0618, USA
* To whom correspondence should be addressed at: 1241 E. Catherine, 4909 Buhl, University of Michigan, Ann Arbor, MI 48109, USA. Tel: +1 7346150456; Fax: +1 7347633784; Email: moranj{at}umich.edu
Received June 16, 2005; Revised August 17, 2005; Accepted September 15, 2005
Long interspersed elements (LINE-1s or L1s) are abundant non-LTR retrotransposons that mobilize through an RNA intermediate by target site primed reverse transcription. The L1-encoded proteins (ORF1p and ORF2p) preferentially associate with their encoding transcript to form a ribonucleoprotein particle (RNP), which is a proposed retrotransposition intermediate. Here, we have used epitope tagging to discriminate the proteins encoded by engineered L1s from those encoded by endogenously expressed L1s. We demonstrate that an L1 containing an epitope tag at the carboxyl terminus of ORF1p remains retrotransposition-competent and that tagged ORF1p and its encoding RNA localize to cytoplasmic RNPs. We also identified two classes of ORF1p mutants, one that severely decreased RNP formation and blocked retrotransposition, and another that allows RNP formation but reduces retrotransposition by 100-fold. Thus, these data indicate that RNP formation is important but not sufficient for L1 retrotransposition and suggest that ORF1p also may function at downstream steps in the L1 retrotransposition pathway.
![]()
CiteULike
Connotea
Del.icio.us What's this?
This article has been cited by other articles:
![]() |
V. P. Belancio, D. J. Hedges, and P. Deininger Mammalian non-LTR retrotransposons: For better or worse, in sickness and in health Genome Res., March 1, 2008; 18(3): 343 - 358. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Chung, O. Siol, T. Dingermann, and T. Winckler Protein Interactions Involved in tRNA Gene-Specific Integration of Dictyostelium discoideum Non-Long Terminal Repeat Retrotransposon TRE5-A Mol. Cell. Biol., December 15, 2007; 27(24): 8492 - 8501. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Januszyk, P. W.-l. Li, V. Villareal, D. Branciforte, H. Wu, Y. Xie, J. Feigon, J. A. Loo, S. L. Martin, and R. T. Clubb Identification and Solution Structure of a Highly Conserved C-terminal Domain within ORF1p Required for Retrotransposition of Long Interspersed Nuclear Element-1 J. Biol. Chem., August 24, 2007; 282(34): 24893 - 24904. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. E. Dmitriev, D. E. Andreev, I. M. Terenin, I. A. Olovnikov, V. S. Prassolov, W. C. Merrick, and I. N. Shatsky Efficient Translation Initiation Directed by the 900-Nucleotide-Long and GC-Rich 5' Untranslated Region of the Human Retrotransposon LINE-1 mRNA Is Strictly Cap Dependent Rather than Internal Ribosome Entry Site Mediated Mol. Cell. Biol., July 1, 2007; 27(13): 4685 - 4697. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. L. Garcia-Perez, M. C.N. Marchetto, A. R. Muotri, N. G. Coufal, F. H. Gage, K. S. O'Shea, and J. V. Moran LINE-1 retrotransposition in human embryonic stem cells Hum. Mol. Genet., July 1, 2007; 16(13): 1569 - 1577. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. L. Garcia-Perez, A. J. Doucet, A. Bucheton, J. V. Moran, and N. Gilbert Distinct mechanisms for trans-mediated mobilization of cellular RNAs by the LINE-1 reverse transcriptase Genome Res., May 1, 2007; 17(5): 602 - 611. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Muckenfuss, M. Hamdorf, U. Held, M. Perkovic, J. Lower, K. Cichutek, E. Flory, G. G. Schumann, and C. Munk APOBEC3 Proteins Inhibit Human LINE-1 Retrotransposition J. Biol. Chem., August 4, 2006; 281(31): 22161 - 22172. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Matsumoto, M. Hamada, M. Osanai, and H. Fujiwara Essential Domains for Ribonucleoprotein Complex Formation Required for Retrotransposition of Telomere-Specific Non-Long Terminal Repeat Retrotransposon SART1. Mol. Cell. Biol., July 1, 2006; 26(13): 5168 - 5179. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Kubo, M. d. C. Seleme, H. S. Soifer, J. L. G. Perez, J. V. Moran, H. H. Kazazian Jr., and N. Kasahara L1 retrotransposition in nondividing and primary human somatic cells PNAS, May 23, 2006; 103(21): 8036 - 8041. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. d. C. Seleme, M. R. Vetter, R. Cordaux, L. Bastone, M. A. Batzer, and H. H. Kazazian Jr. Extensive individual variation in L1 retrotransposition capability contributes to human genetic diversity PNAS, April 25, 2006; 103(17): 6611 - 6616. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. P. Belancio, D. J. Hedges, and P. Deininger LINE-1 RNA splicing and influences on mammalian gene expression Nucleic Acids Res., March 22, 2006; 34(5): 1512 - 1521. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. W.-L. Li, J. Li, S. L. Timmerman, L. A. Krushel, and S. L. Martin The dicistronic RNA from the mouse LINE-1 retrotransposon contains an internal ribosome entry site upstream of each ORF: implications for retrotransposition Nucleic Acids Res., February 6, 2006; 34(3): 853 - 864. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. S. Alisch, J. L. Garcia-Perez, A. R. Muotri, F. H. Gage, and J. V. Moran Unconventional translation of mammalian LINE-1 retrotransposons Genes & Dev., January 15, 2006; 20(2): 210 - 224. [Abstract] [Full Text] [PDF] |
||||






