Codon optimality in cancer.
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
received:
16
07
2021
accepted:
10
09
2021
revised:
24
08
2021
pubmed:
30
9
2021
medline:
30
12
2021
entrez:
29
9
2021
Statut:
ppublish
Résumé
A key characteristic of cancer cells is their increased proliferative capacity, which requires elevated levels of protein synthesis. The process of protein synthesis involves the translation of codons within the mRNA coding sequence into a string of amino acids to form a polypeptide chain. As most amino acids are encoded by multiple codons, the nucleotide sequence of a coding region can vary dramatically without altering the polypeptide sequence of the encoded protein. Although mutations that do not alter the final amino acid sequence are often thought of as silent/synonymous, these can still have dramatic effects on protein output. Because each codon has a distinct translation elongation rate and can differentially impact mRNA stability, each codon has a different degree of 'optimality' for protein synthesis. Recent data demonstrates that the codon preference of a transcriptome matches the abundance of tRNAs within the cell and that this supply and demand between tRNAs and mRNAs varies between different cell types. The largest observed distinction is between mRNAs encoding proteins associated with proliferation or differentiation. Nevertheless, precisely how codon optimality and tRNA expression levels regulate cell fate decisions and their role in malignancy is not fully understood. This review describes the current mechanistic understanding on codon optimality, its role in malignancy and discusses the potential to target codon optimality therapeutically in the context of cancer.
Identifiants
pubmed: 34584217
doi: 10.1038/s41388-021-02022-x
pii: 10.1038/s41388-021-02022-x
pmc: PMC8585667
doi:
Substances chimiques
Codon
0
RNA, Messenger
0
RNA, Transfer
9014-25-9
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
6309-6320Subventions
Organisme : Medical Research Council
ID : MC_EX_G0902052
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UP_A600_1024
Pays : United Kingdom
Organisme : Cancer Research UK (CRUK)
ID : A29252
Informations de copyright
© 2021. The Author(s).
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