Effect of mRNA/tRNA mutations on translation speed: Implications for human diseases

J Biol Chem. 2023 Sep;299(9):105089. doi: 10.1016/j.jbc.2023.105089. Epub 2023 Jul 24.

Abstract

Recent discoveries establish tRNAs as central regulators of mRNA translation dynamics, and therefore cotranslational folding and function of the encoded protein. The tRNA pool, whose composition and abundance change in a cell- and tissue-dependent manner, is the main factor which determines mRNA translation velocity. In this review, we discuss a group of pathogenic mutations, in the coding sequences of either protein-coding genes or in tRNA genes, that alter mRNA translation dynamics. We also summarize advances in tRNA biology that have uncovered how variations in tRNA levels on account of genetic mutations affect protein folding and function, and thereby contribute to phenotypic diversity in clinical manifestations.

Keywords: SNPs; codon; mRNA; mRNA translation; pathogenic mutations; tRNA; tRNA abundance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Codon / genetics
  • Humans
  • Mutation*
  • Polymorphism, Single Nucleotide
  • Protein Biosynthesis* / genetics
  • RNA, Messenger* / genetics
  • RNA, Messenger* / metabolism
  • RNA, Transfer* / genetics
  • RNA, Transfer* / metabolism
  • Time Factors

Substances

  • Codon
  • RNA, Messenger
  • RNA, Transfer