Cooperativity between different tRNA modifications and their modification pathways

Biochim Biophys Acta Gene Regul Mech. 2018 Apr;1861(4):409-418. doi: 10.1016/j.bbagrm.2017.12.003. Epub 2017 Dec 5.


Ribonucleotide modifications perform a wide variety of roles in synthesis, turnover and functionality of tRNA molecules. The presence of particular chemical moieties can refine the internal interaction network within a tRNA molecule, influence its thermodynamic stability, contribute novel chemical properties and affect its decoding behavior during mRNA translation. As the lack of specific modifications in the anticodon stem and loop causes disrupted proteome homeostasis, diminished response to stress conditions, and the onset of human diseases, the underlying modification cascades have recently gained particular scientific and clinical interest. Nowadays, a complicated but conclusive image of the interconnectivity between different enzymatic modification cascades and their resulting tRNA modifications emerges. Here we summarize the current knowledge in the field, focusing on the known instances of cross talk among the enzymatic tRNA modification pathways and the consequences on the dynamic regulation of the tRNA modificome by various factors. This article is part of a Special Issue entitled: SI: Regulation of tRNA synthesis and modification in physiological conditions and disease edited by Dr. Boguta Magdalena.

Keywords: Anticodon stem and loop; Cross talk; Elongator; Neurodegenerative diseases; Yeast; tRNA modifications.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anticodon / genetics
  • Endoribonucleases / metabolism
  • Eukaryotic Cells / metabolism
  • Humans
  • Mitochondrial Diseases / genetics
  • Mitochondrial Diseases / metabolism
  • Models, Molecular
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Nervous System Diseases / genetics
  • Nervous System Diseases / metabolism
  • Nucleic Acid Conformation
  • Protein Biosynthesis
  • RNA Processing, Post-Transcriptional*
  • RNA Stability
  • RNA, Fungal / genetics
  • RNA, Fungal / metabolism
  • RNA, Neoplasm / metabolism
  • RNA, Transfer / genetics
  • RNA, Transfer / metabolism*
  • RNA-Binding Proteins / metabolism
  • Saccharomyces cerevisiae Proteins / metabolism
  • Schizosaccharomyces pombe Proteins / metabolism
  • Uridine / analogs & derivatives
  • Uridine / genetics
  • tRNA Methyltransferases / metabolism


  • Anticodon
  • Multiprotein Complexes
  • RNA, Fungal
  • RNA, Neoplasm
  • RNA-Binding Proteins
  • Saccharomyces cerevisiae Proteins
  • Schizosaccharomyces pombe Proteins
  • RNA, Transfer
  • tRNA Methyltransferases
  • Endoribonucleases
  • Uridine