User:Walternmoss/R2 retrotransposon

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R2 elements are ancient molecular parasites found throughout arthropods. The R2 element is a type of retrotransposon: a transposon whose reproduction proceeds through an RNA intermediate (similar to retroviruses). Three regions of conserved secondary structure appear in the R2 RNA; secondary structure is known or suspected to be important in several aspect of R2 biology: RNA processing, genome incorporation (retrotransposition), and translation.

RNA Processing: The R2 Ribozyme

The R2 element is co-transcribed with host organism 28S ribosomal RNA (rRNA). To become a fully mature R2 messenger RNA (mRNA), requires that the initial R2 transcript be processed to remove the 28S rRNA. This occurs by a self cleaving ribozyme (RNA enzyme) that occurs close to the R2/rRNA junction site. The R2 ribozyme has marked structural and sequence correspondence to the Hepatitis Delta Virus (HDV) ribozyme. (REF)

The mature R2 mRNA contains a single open reading frame (ORF) for the multi-functional R2 protein, and two untranslated regions(UTRs) at the 5' and 3' ends.

Genome Integration: The 5' and 3' R2 RNA structured regions

R2 elements reproduce by site specific integration into host genome 28S rRNA genes^[1]. Integration proceeds by a sequence of DNA strand cleavage and DNA synthesis mediated by a RNA-protein complex made up of two R2 proteins, bound to the mRNA at the 5' and 3' structured regions, and a single R2 mRNA^[2],^[3]. The mRNA-protein complex recognizes the insertion site in the 28S rRNA gene. The 3′ bound R2 protein nicks one DNA strand providing a 3′-OH group to prime reverse-transcription of the R2 complementary DNA(cDNA). The 5' bound R2 protein then cleaves the other DNA strand ^[4]and acts as a DNA templated DNA polymerase, using the R2 cDNA as template^[5].

The 3′ R2 protein binding site occurs within the mRNA UTR and has a conserved secondary structure determined from thermodynmamic energy minimization, sequence comparison and structure probing with chemical reagents^[6]. Secondary structure conservation occurs within silk moths, drosophila and between the two groups.

The 5′ R2 protein binding site (in Bombyx mori) occurs in a region that spans part of the 5' UTR and the start of the R2 ORF. These region also has a conserved secondary structure, which has been deduced from binding to oligonucleotide microarrays, structure probing, and free energy minimization^[7]. To date, conservation of structure has only been described between silk moth species.

R2 Translation (putative): The R2 Pseudoknot

Within the 5' structure of B. mori, 74 nucleotides fold into a complex RNA pseudoknot, which is supported by NMR spectra^[8] and sequence comparison. Pseudoknots are unusual structural elements and they often play important roles in biological processes^[9]. Alignments of R2 RNA and predicted R2 ORFs suggests a transition from functions relating solely to RNA secondary structure to protein coding potential only. Alignments also suggest the possibility of an unusual mode of translation initiation: as the R2 transcript has no 5' cap structure, has multiple in-frame stop codons in its 5' region, and from the observation that conservation of the protein coding sequence only occurs after the conserved pseudoknot^[10]. Cartoon of R2 5' structure

It is possible that this structure, alone or with other parts of the 5' conserved region, may be able to recruit the ribosome in a process similar to internal ribosomal entry sites (IRES).

References

^ Eickbush, T. H. (2002). R2 and Related Site-specific non-LTR Retrotransposons. In Mobile DNA II (N. Craig, R. C., M. Gellert, and A. Lambowitz, ed.), pp. 813-835. American Society of Microbiology Press, Washington D.C.
^ Luan, D. D., Korman, M. H., Jakubczak, J. L. & Eickbush, T. H. (1993). Reverse transcription of R2Bm RNA is primed by a nick at the chromosomal target site: a mechanism for non-LTR retrotransposition. Cell 72, 595-605.
^ Yang, J., Malik, H. S. & Eickbush, T. H. (1999). Identification of the endonuclease domain encoded by R2 and other site-specific, non-long terminal repeat retrotransposable elements. Proc Natl Acad Sci U S A 96, 7847-52.
^ Christensen, SM, Ye, J & Eickbush, TH (2006). RNA from the 5' end of the R2 retrotransposon controls R2 protein binding to and cleavage of its DNA target site. Proc Natl Acad Sci U S A 103, 17602-7.
^ Kurzynska-Kokorniak, A., Jamburuthugoda, V. K., Bibillo, A. & Eickbush, T. H. (2007). DNA-directed DNA polymerase and strand displacement activity of the reverse transcriptase encoded by the R2 retrotransposon. J Mol Biol 374, 322-33.
^ Ruschak AM, Mathews DH, Bibillo A, et al. (2004). "Secondary structure models of the 3' untranslated regions of diverse R2 RNAs". RNA 10 (6): 978–87.
^ Kierzek, E., Kierzek, R., Moss, W. N., Christensen, S. M., Eickbush, T. H. & Turner, D. H. (2008). 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 Res 36, 1770-82.
^ Hart, J. M., Kennedy, S. D., Mathews, D. H. & Turner, D. H. (2008). NMR-assisted prediction of RNA secondary structure: identification of a probable pseudoknot in the coding region of an R2 retrotransposon. J Am Chem Soc 130, 10233-9.
^ Liu, B, Mathews, D.H., & Turner, D.H. (2010) "RNA pseudoknots: folding and finding". Biology Reports 2:8.
^ Kierzek E., Christensen S.M., Eickbush T.H., Kierzek R., Turner D.H., Moss W.N. 2009. Secondary structures for 5’ regions of R2 retrotransposon RNAs reveal a novel conserved pseudoknot and regions that evolve under different constraints. J Mol Biol 390: 428–442.

External links

Page for R2 RNA element at Rfam

Category:Cis-regulatory RNA elements

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[1] Eickbush, T. H. (2002). R2 and Related Site-specific non-LTR Retrotransposons. In Mobile DNA II (N. Craig, R. C., M. Gellert, and A. Lambowitz, ed.), pp. 813-835. American Society of Microbiology Press, Washington D.C.

[2] Luan, D. D., Korman, M. H., Jakubczak, J. L. & Eickbush, T. H. (1993). Reverse transcription of R2Bm RNA is primed by a nick at the chromosomal target site: a mechanism for non-LTR retrotransposition. Cell 72, 595-605.

[3] Yang, J., Malik, H. S. & Eickbush, T. H. (1999). Identification of the endonuclease domain encoded by R2 and other site-specific, non-long terminal repeat retrotransposable elements. Proc Natl Acad Sci U S A 96, 7847-52.

[4] Christensen, SM, Ye, J & Eickbush, TH (2006). RNA from the 5' end of the R2 retrotransposon controls R2 protein binding to and cleavage of its DNA target site. Proc Natl Acad Sci U S A 103, 17602-7.

[5] Kurzynska-Kokorniak, A., Jamburuthugoda, V. K., Bibillo, A. & Eickbush, T. H. (2007). DNA-directed DNA polymerase and strand displacement activity of the reverse transcriptase encoded by the R2 retrotransposon. J Mol Biol 374, 322-33.

[6] Ruschak AM, Mathews DH, Bibillo A, et al. (2004). "Secondary structure models of the 3' untranslated regions of diverse R2 RNAs". RNA 10 (6): 978–87.

[7] Kierzek, E., Kierzek, R., Moss, W. N., Christensen, S. M., Eickbush, T. H. & Turner, D. H. (2008). 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 Res 36, 1770-82.

[8] Hart, J. M., Kennedy, S. D., Mathews, D. H. & Turner, D. H. (2008). NMR-assisted prediction of RNA secondary structure: identification of a probable pseudoknot in the coding region of an R2 retrotransposon. J Am Chem Soc 130, 10233-9.

[9] Liu, B, Mathews, D.H., & Turner, D.H. (2010) "RNA pseudoknots: folding and finding". Biology Reports 2:8.

[10] Kierzek E., Christensen S.M., Eickbush T.H., Kierzek R., Turner D.H., Moss W.N. 2009. Secondary structures for 5’ regions of R2 retrotransposon RNAs reveal a novel conserved pseudoknot and regions that evolve under different constraints. J Mol Biol 390: 428–442.

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