Thomas H. Eickbush

Professor

Contact Information:

University of Rochester
Department of Biology

River Campus Box 270211
Rochester, New York 14627-0211

Hutchison 334A (office)
Hutchison 328 (lab)

(585) 275-7247 (office)
(585) 275-8362 (lab)

Research Overview

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.

Figure1
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/

Selected Publications

  • A population genetic model for the maintenance of R2 retrotransposons in rRNA gene loci. Zhou J, Eickbush MT, Eickbush TH. PLoS Genet. 2013 Jan;9(1):e1003179. doi: 10.1371/journal.pgen.1003179. Epub 2013 Jan 10. PMID: 23326244 [PubMed]
  • Y chromosome mediates ribosomal DNA silencing and modulates the chromatin state in Drosophila. Zhou J, Sackton TB, Martinsen L, Lemos B, Eickbush TH, Hartl DL.Proc Natl Acad Sci U S A. 2012 Jun 19;109(25):9941-6. Epub 2012 Jun 4.PMID: 22665801 [PubMed]
  • R2 and R2/R1 hybrid non-autonomous retrotransposons derived by internal deletions of full-length elements. Eickbush DG, Eickbush TH.Mob DNA. 2012 May 23;3(1):10. doi: 10.1186/1759-8753-3-10.PMID: 22621441 [PubMed]
  • Heterochromatin formation promotes longevity and represses ribosomal RNA synthesis. Larson K, Yan SJ, Tsurumi A, Liu J, Zhou J, Gaur K, Guo D, Eickbush TH, Li WX.PLoS Genet. 2012 Jan;8(1):e1002473. Epub 2012 Jan 26.PMID: 22291607 [PubMed - indexed for MEDLINE]
  • Retrotransposition of R2 elements in somatic nuclei during the early development of Drosophila. Eickbush MT, Eickbush TH.Mob DNA. 2011 Sep 29;2(1):11. doi: 10.1186/1759-8753-2-11.PMID: 21958913 [PubMed]
  • The R2 retrotransposon RNA families. Moss WN, Eickbush DG, Lopez MJ, Eickbush TH, Turner DH.RNA Biol. 2011 Sep-Oct;8(5):714-8. Epub 2011 Jul 7.PMID: 21734471 [PubMed]
  • The reverse transcriptase encoded by the non-LTR retrotransposon R2 is as error-prone as that encoded by HIV-1. Jamburuthugoda VK, Eickbush TH.J Mol Biol. 2011 Apr 15;407(5):661-72. Epub 2011 Feb 12.PMID: 21320510 [PubMed]
  • R2 retrotransposons encode a self-cleaving ribozyme for processing from an rRNA cotranscript. Eickbush DG, Eickbush TH.Mol Cell Biol. 2010 Jul;30(13):3142-50. Epub 2010 Apr 26.PMID: 20421411 [PubMed - indexed for MEDLINE]
  • Welcome to mobile DNA. Craig NL, Eickbush TH, Voytas DF.Mob DNA. 2010 Jan 25;1(1):1. No abstract available.PMID: 20226071 [PubMed]
  • Maintenance of multiple lineages of R1 and R2 retrotransposable elements in the ribosomal RNA gene loci of Nasonia. Stage DE, Eickbush TH.Insect Mol Biol. 2010 Feb;19 Suppl 1:37-48.PMID: 20167016 [PubMed - indexed for MEDLINE]
  • Origin of nascent lineages and the mechanisms used to prime second-strand DNA synthesis in the R1 and R2 retrotransposons of Drosophila. Stage DE, Eickbush TH.Genome Biol. 2009;10(5):R49. Epub 2009 May 5.PMID: 19416522 [PubMed - indexed for MEDLINE]
  • Secondary structures for 5′ regions of R2 retrotransposon RNAs reveal a novel conserved pseudoknot and regions that evolve under different constraints. Kierzek E, Christensen SM, Eickbush TH, Kierzek R, Turner DH, Moss WN.J Mol Biol. 2009 Jul 17;390(3):428-42. Epub 2009 May 3.PMID: 19397915 [PubMed - indexed for MEDLINE]
  • The pattern of R2 retrotransposon activity in natural populations of Drosophila simulans reflects the dynamic nature of the rDNA locus. Zhou J, Eickbush TH.PLoS Genet. 2009 Feb;5(2):e1000386. Epub 2009 Feb 20.PMID: 19229317 [PubMed - indexed for MEDLINE]
  • Role of recombination in the long-term retention of transposable elements in rRNA gene loci .Zhang X, Eickbush MT, Eickbush TH.Genetics. 2008 Nov;180(3):1617-26. Epub 2008 Sep 14.PMID: 18791229 [PubMed - indexed for MEDLINE]
  • Epigenetic regulation of retrotransposons within the nucleolus of Drosophila. Eickbush DG, Ye J, Zhang X, Burke WD, Eickbush TH.Mol Cell Biol. 2008 Oct;28(20):6452-61. Epub 2008 Aug 4.PMID: 18678644 [PubMed - indexed for MEDLINE]
  • The diversity of retrotransposons and the properties of their reverse transcriptases. Eickbush TH, Jamburuthugoda VK.Virus Res. 2008 Jun;134(1-2):221-34. Epub 2008 Feb 7. Review.PMID: 18261821 [PubMed - indexed for MEDLINE]
  • Isoenergetic penta- and hexanucleotide microarray probing and chemical mapping provide a secondary structure model for an RNA element orchestrating R2 retrotransposon protein function. Kierzek E, Kierzek R, Moss WN, Christensen SM, Eickbush TH, Turner DH.Nucleic Acids Res. 2008 Apr;36(6):1770-82. Epub 2008 Feb 5.PMID: 18252773 [PubMed - indexed for MEDLINE]
  • Rapid R2 retrotransposition leads to the loss of previously inserted copies via large deletions of the rDNA locus. Zhang X, Zhou J, Eickbush TH.Mol Biol Evol. 2008 Jan;25(1):229-37. Epub 2007 Nov 13.PMID: 18003600 [PubMed - indexed for MEDLINE]