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General Conclusion

  • Naohiro TerasakaEmail author
Chapter
  • 174 Downloads
Part of the Springer Theses book series (Springer Theses)

Abstract

In natural, each ARS specifically recognizes each tRNA and amino acid, and tRNAs are specifically aminoacylated with cognate amino acids by cognate ARSs. On the other hand, flexizymes, which are in vitro selected aminoacylation ribozymes, enable to aminoacylate RNAs bearing various 3′-ends with various amino acids including both canonical and noncanonical amino acids. By utilizing these unique characteristics, novel interaction between folic acid and hsa-pre-miR-125a was discovered (Chap.  2), and an orthogonal ribosome–tRNA pair was developed by engineering of peptidyl transferase center (Chap.  3). Aminoacylation at 3′-end of RNA with various amino acids by flexizymes has a great potential to be applied for various RNA studies including analysis of translation mechanisms, engineering of translation, discoveries of novel small ncRNAs.

Keywords

Ribozyme MicroRNA SELEX tRNA Ribosome Translation 

References

  1. Bose D, Jayaraj G, Suryawanshi H, Agarwala P, Pore SK, Banerjee R, Maiti S (2012) The tuberculosis drug streptomycin as a potential cancer therapeutic: inhibition of miR-21 function by directly targeting its precursor. Angew Chem Int Ed Engl 51(4):1019–1023. doi: 10.1002/anie.201106455 CrossRefGoogle Scholar
  2. Chen XG, Sim S, Wurtmann EJ, Feke A, Wolin SL (2014) Bacterial noncoding Y RNAs are widespread and mimic tRNAs. RNA 20(11):1715–1724. doi: 10.1261/rna.047241.114 CrossRefGoogle Scholar
  3. Fried SD, Schmied WH, Uttamapinant C, Chin JW (2015) Ribosome subunit stapling for orthogonal translation in E. coli. Angew Chem Int Edit 54(43):12791–12794. doi: 10.1002/anie.201506311
  4. Liu J, Liu M, Horowitz J (1998) Recognition of the universally conserved 3′-CCA end of tRNA by elongation factor EF-Tu. RNA 4(6):639–646. doi: 10.1017/S1355838298980013 CrossRefGoogle Scholar
  5. Morimoto J, Hayashi Y, Suga H (2012) Discovery of macrocyclic peptides armed with a mechanism-based warhead: isoform-selective inhibition of human deacetylase SIRT2. Angew Chem Int Ed Engl 51(14):3423–3427. doi: 10.1002/ange.201108118 CrossRefGoogle Scholar
  6. Neumann H, Wang K, Davis L, Garcia-Alai M, Chin JW (2010) Encoding multiple unnatural amino acids via evolution of a quadruplet-decoding ribosome. Nature 464(7287):441–444. doi: 10.1038/nature08817 CrossRefGoogle Scholar
  7. Orelle C, Carlson ED, Szal T, Florin T, Jewett MC, Mankin AS (2015) Protein synthesis by ribosomes with tethered subunits. Nature 524(7563):119–289. doi: 10.1038/nature14862 CrossRefGoogle Scholar
  8. Rackham O, Chin JW (2005) A network of orthogonal ribosome ∙ mRNA pairs. Nat Chem Biol 1(3):159–166. doi: 10.1038/Nchembio719 CrossRefGoogle Scholar
  9. Saito H, Kourouklis D, Suga H (2001a) An in vitro evolved precursor tRNA with aminoacylation activity. EMBO J 20(7):1797–1806. doi: 10.1093/emboj/20.7.1797 CrossRefGoogle Scholar
  10. Saito H, Watanabe K, Suga H (2001b) Concurrent molecular recognition of the amino acid and tRNA by a ribozyme. RNA 7(12):1867–1878Google Scholar
  11. Sunwoo H, Dinger ME, Wilusz JE, Amaral PP, Mattick JS, Spector DL (2009) MEN ε/β nuclear-retained noncoding RNAs are up-regulated upon muscle differentiation and are essential components of paraspeckles. Genome Res 19(3):347–359. doi: 10.1101/gr.087775.108 CrossRefGoogle Scholar
  12. Terasaka N, Suga H (2014) Flexizymes-facilitated genetic code reprogramming leading to the discovery of drug-like peptides. Chem Lett 43(1):11–19. doi: 10.1246/Cl.130910 CrossRefGoogle Scholar
  13. Terasaka N, Hayashi G, Katoh T, Suga H (2014) An orthogonal ribosome–tRNA pair via engineering of the peptidyl transferase center. Nat Chem Biol 10(7):555–557. doi: 10.1038/nchembio.1549 CrossRefGoogle Scholar
  14. Velagapudi SP, Gallo SM, Disney MD (2014) Sequence-based design of bioactive small molecules that target precursor microRNAs. Nat Chem Biol 10(4):291–297. doi: 10.1038/Nchembio.1452 CrossRefGoogle Scholar
  15. Virumae K, Saarma U, Horowitz J, Remme J (2002) Functional importance of the 3′-terminal adenosine of tRNA in ribosomal translation. J Biol Chem 277(27):24128–24134. doi: 10.1074/jbc.M200393200 CrossRefGoogle Scholar
  16. Wang KH, Neumann H, Peak-Chew SY, Chin JW (2007) Evolved orthogonal ribosomes enhance the efficiency of synthetic genetic code expansion. Nat Biotechnol 25(7):770–777. doi: 10.1038/Nbt1314 CrossRefGoogle Scholar
  17. Wilusz JE, Freier SM, Spector DL (2008) 3′ end processing of a long nuclear-retained noncoding RNA yields a tRNA-like cytoplasmic RNA. Cell 135(5):919–932. doi: 10.1016/j.cell.2008.10.012 CrossRefGoogle Scholar
  18. Wilusz JE, Whipple JM, Phizicky EM, Sharp PA (2011) tRNAs marked with CCACCA are targeted for degradation. Science 334(6057):817–821. doi: 10.1126/science.1213671 CrossRefGoogle Scholar

Copyright information

© Springer Japan KK 2017

Authors and Affiliations

  1. 1.ETH ZurichZurichSwitzerland

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