The Eickbush laboratory studies the mechanism of integration, cellular control, and population genetics of mobile elements that insert specifically into the 28S rRNA genes of their hosts. Most of our work focuses on the R2 retrotransposon; elements found in animals as diverse as vertebrates, arthropods, and hydra. Our early biochemical studies of the proteins encoded by R2 revealed a new mechanism of insertion (retrotransposition) in which the element's RNA transcript is directly reverse transcribed using the chromosomal target site as primer. A large family of mobile elements, the non-LTR retrotransposons, is now thought to use this Target Primed Reverse Transcription (TPRT) mechanism. Non-LTR retrotransposon insertions have had dramatic effects on the evolution and current functioning of eukaryotic genomes. For example, the TPRT mechanism has been estimated to account for 40% of the DNA in the human genome.
Strong selective pressure should eliminate R2 elements from the rDNA locus, because every R2 insertion blocks the production of functional 28S rRNA. Individual R2 copies are rapidly eliminated by the frequent recombination events that lead to the concerted evolution of the rRNA genes. However, studies of the abundance of R2 elements within populations, as well as the phylogenetic studies of R2 elements in different species, suggest R2 elements are seldom completely lost, and as a group undergo highly stable transmission over millions of years. Our current studies focus on the balance that must exist between the rate of new R2 insertions to preserve the element and their rate of loss by recombination and selection. We are also dissecting the mechanisms that control R2 activity using active and inactive lines of Drosophila. R2 elements are co-transcribed with the rRNA genes and are processed from this co-transcript by a self-cleaving ribozyme encoded at the 5’ end of R2. Primary control over R2 is at the level of transcription of the rDNA unit. Our studies have shown that R2 transcription is influenced by the genes involved in heterochromatin formation, but ultimately it is the distribution of R2-inserted units in the rDNA locus that controls whether R2-inserted units are transcribed. Current studies are designed to determine both when and how the R2 protein is translated from the self-cleaved RNA, and thus when during development R2 elements retrotranspose. For more information go to our lab website http://blogs.rochester.edu/EickbushLab/
- Montiel EE, Cabrero J, Ruiz-Estévez M, Burke WD, Eickbush TH, Camacho JP, López-León MD. 2014 Mar 14. Preferential occupancy of R2 retroelements on the B chromosomes of the grasshopper Eyprepocnemisplorans. PLoS One9(3):e91820. doi: 10.1371/journal.pone.0091820. eCollection 2014. PMID: 24632855 [PubMed - in process] Free PMC Article
- Jamburuthugoda VK, Eickbush TH. 2014. Identification of RNA binding motifs in the R2 retrotransposon-encoded reverse transcriptase.Nucleic Acids Res42(13):8405-15. doi: 10.1093/nar/gku514. Epub 2014 Jun 23. PMID: 24957604 [PubMed - in process] Free PMC Article
- Eickbush DG, Burke WD, Eickbush TH. 2013 Sep 16. Evolution of the r2 retrotransposon ribozyme and its self-cleavage site. PLoS OneE8(9):e66441.doi:10.1371/journal.pone.0066441.PMID:24066021 Free PMC Article
- Zhou J, Eickbush MT, Eickbush TH. 2013 Jan. A population genetic model for the maintenance of R2 retrotransposons in rRNA gene loci.PLoS Genet 9(1):e1003179. doi: 10.1371/journal.pgen.1003179. Epub 2013 Jan 10. PMID: 23326244 [PubMed]
- Zhou J, Sackton TB, Martinsen L, Lemos B, Eickbush TH, Hartl DL. 2012 Jun 19. Y chromosome mediates ribosomal DNA silencing and modulates the chromatin state inDrosophila. Proc Natl Acad Sci U S A 109(25):9941-6. Epub 2012 Jun 4.PMID: 22665801 (PubMed)
- Eickbush DG, Eickbush TH. 2012 May 23. R2 and R2/R1 hybrid non-autonomous retrotransposons derived by internal deletions of full-length elements. Mob DNA3(1):10. doi: 10.1186/1759-8753-3-10.PMID: 22621441 [PubMed]
- Larson K, Yan SJ, Tsurumi A, Liu J, Zhou J, Gaur K, Guo D, Eickbush TH, Li WX. 2012 Jan. Heterochromatin formation promotes longevity and represses ribosomal RNA synthesis. PLoS Genet8(1):e1002473. Epub 2012 Jan 26.PMID: 22291607 [PubMed - indexed for MEDLINE]
- Eickbush MT, Eickbush TH. 2011 Sep 29. Retrotransposition of R2 elements in somatic nuclei during the early development ofDrosophila. Mob DNA2(1):11. doi: 10.1186/1759-8753-2-11.PMID: 21958913 [PubMed]
- Moss WN, Eickbush DG, Lopez MJ, Eickbush TH, Turner DH. 2011 Sep-Oct. The R2 retrotransposon RNA families. RNA Biol8(5):714-8. Epub 2011 Jul 7.PMID: 21734471 [PubMed]
- Jamburuthugoda VK, Eickbush TH. 2011 Apr 15. The reverse transcriptase encoded by the non-LTR retrotransposon R2 is as error-prone as that encoded by HIV-1. J Mol Biol407(5):661-72. Epub 2011 Feb 12.PMID: 21320510 [PubMed]
- Eickbush DG, Eickbush TH. 2010 Jul. R2 retrotransposons encode a self-cleaving ribozyme for processing from an rRNA cotranscript. Mol Cell Biol30(13):3142-50. Epub 2010 Apr 26.PMID: 20421411 [PubMed - indexed for MEDLINE]
- Craig NL, Eickbush TH, Voytas DF. 2010 Jan 25. Welcome to mobile DNA. Mob DNA1(1):1. No abstract available.PMID: 20226071 [PubMed]
- Stage DE, Eickbush TH. 2010 Feb. Maintenance of multiple lineages of R1 and R2 retrotransposable elements in the ribosomal RNA gene loci of Nasonia. Insect Mol Biol 19 Suppl 1:37-48.PMID: 20167016 [PubMed - indexed for MEDLINE]
- Stage DE, Eickbush TH. 2009. Origin of nascent lineages and the mechanisms used to prime second-strand DNA synthesis in the R1 and R2 retrotransposons of Drosophila. Genome Biol10(5):R49. Epub 2009 May 5.PMID: 19416522 [PubMed - indexed for MEDLINE]
- Kierzek E, Christensen SM, Eickbush TH, Kierzek R, Turner DH, Moss WN. 2009 Jul 17. Secondary structures for 5′ regions of R2 retrotransposon RNAs reveal a novel conserved pseudoknot and regions that evolve under different constraints. J Mol Biol390(3):428-42. Epub 2009 May 3.PMID: 19397915 [PubMed - indexed for MEDLINE]
- Zhou J, Eickbush TH. 2009 Feb. The pattern of R2 retrotransposon activity in natural populations of Drosophila simulans reflects the dynamic nature of the rDNA locus. PLoS Genet5(2):e1000386. Epub 2009 Feb 20.PMID: 19229317 [PubMed - indexed for MEDLINE]
- Zhang X, Eickbush MT, Eickbush TH. 2008 Nov. Role of recombination in the long-term retention of transposable elements in rRNA gene loci. Genetics180(3):1617-26. Epub 2008 Sep 14.PMID: 18791229 [PubMed - indexed for MEDLINE]
- Eickbush DG, Ye J, Zhang X, Burke WD, Eickbush TH. 2008 Oct. Epigenetic regulation of retrotransposons within the nucleolus of Drosophila. Mol Cell Biol28(20):6452-61. Epub 2008 Aug 4.PMID: 18678644 [PubMed - indexed for MEDLINE]
- Eickbush TH, Jamburuthugoda VK. 2008 Jun. The diversity of retrotransposons and the properties of their reverse transcriptases. Virus Res134(1-2):221-34. Epub 2008 Feb 7. Review.PMID: 18261821 [PubMed - indexed for MEDLINE]
- Kierzek E, Kierzek R, Moss WN, Christensen SM, Eickbush TH, Turner DH. 2008 Apr. Isoenergetic penta- and hexanucleotide microarray probing and chemical mapping provide a secondary structure model for an RNA element orchestrating R2 retrotransposon protein function. Nucleic Acids Res36(6):1770-82. Epub 2008 Feb 5.PMID: 18252773 [PubMed - indexed for MEDLINE]
- Zhang X, Zhou J, Eickbush TH. 2008 Jan. Rapid R2 retrotransposition leads to the loss of previously inserted copies via large deletions of the rDNA locus. Mol Biol Evol25(1):229-37. Epub 2007 Nov 13.PMID: 18003600 [PubMed - indexed for MEDLINE]
- Drosophila 12 Genomes Consortium, multiple authors. 2007 Evolution of genes and genomes on the Drosophila phylogeny. Nature Nov 8;450(7167):203-18.PMID: 17994087 [PubMed - indexed for MEDLINE]
- Stage DE, Eickbush TH. 2007 Dec. Sequence variation within the rRNA gene loci of 12 Drosophila species. Genome Res17(12):1888-97. Epub 2007 Nov 7.PMID: 17989256 [PubMed - indexed for MEDLINE]
- Kurzynska-Kokorniak A, Jamburuthugoda VK, Bibillo A, Eickbush TH. 2007 Nov 23. DNA-directed DNA polymerase and strand displacement activity of the reverse transcriptase encoded by the R2 retrotransposon. J Mol Biol374(2):322-33. Epub 2007 Sep 20.PMID: 17936300 [PubMed - indexed for MEDLINE]
- 2007. Finely orchestrated movements: evolution of the ribosomal RNA genes.Genetics175: 477-485.
- Christensen, S.M., J.Ye,, and T.H. Eichbush. 2006. RNA from the 5′ end of the R2 retrotransposon controls R2 protein binding to and cleavage of its DNA target site. PNAS PMID: 17105809 [PubMed - indexed for MEDLINE]
- 2006. Chromatin structure and transcription of the R1- and R2-inserted rRNA genes of Drosophila melanogaster.Mol Cell Biol 23: 8781-8790.
- Christensen, S.M., A. Bibillo and T.H. Eickbush. 2005. Role of the Bombyx mori R2 element N-terminal domain in the target-primed reverse transcription (TPRT) reaction. Nucleic Acids Res33(20):6461-8. (PubMed)
- 2005. Monitoring the mode and tempo of concerted evolution in the Drosophila melanogaster rDNA locus. Genetics171: 1837-1846.
- 2005. Characterization of active R2 retrotransposition in the rDNA locus of Drosophila simulans. Genetics170: 195-205.
- 2005. R2 target primed reverse transcription: ordered cleavage and polymerization steps by protein subunits asymmetrically bound to the target DNA. Mol. Cell. Biol25: 6617-6628.
- 2005. Competition between R1 and R2 retrotransposable elements in the 28S rRNA genes of insects. Cytogenetic Genome Res110: 299-306.
- Ruschak, A.M., D.H. Mathews, A. Bibillo, S.L. Spinelli, J.L. Childs, T.H. Eickbush and D.H. Turner. 2004. Secondary Structure models of the 3′ untranslated regions of diverse R2 RNAs. RNA10:978-987. (PubMed)
- Christensen, S. and Eickbush, T. H. 2004. Footprint of the R2Bm protein on its target site before and after cleavage in the presence and absence of RNA. J. Mol. Biol336:1035-1045. (PubMed)
- Bibillo, A. and T.H. Eickbush. 2004. End-to-end template jumping by the reverse transcriptase encoded by the R2 retrotransposon. J. Biol. Chem279:14945-14953. (PubMed)