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Review
. 2021 Feb 18;6(1):68.
doi: 10.1038/s41392-020-00444-9.

The regulation of protein translation and its implications for cancer

Ping Song #  1 , Fan Yang #  2 , Hongchuan Jin  3 , Xian Wang  4
Affiliations
Review

The regulation of protein translation and its implications for cancer

Ping Song et al. Signal Transduct Target Ther. .

Abstract

In addition to the deregulation of gene transcriptions and post-translational protein modifications, the aberrant translation from mRNAs to proteins plays an important role in the pathogenesis of various cancers. Targeting mRNA translation are expected to become potential approaches for anticancer treatments. Protein translation is affected by many factors including translation initiation factors and RNA-binding proteins. Recently, modifications of mRNAs mainly N6-methyladenine (m6A) modification and noncoding RNAs, such as microRNAs and long noncoding RNAs are involved. In this review, we generally summarized the recent advances on the regulation of protein translation by the interplay between mRNA modifications and ncRNAs. By doing so, we hope this review could offer some hints for the development of novel approaches in precision therapy of human cancers.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
The process of gene expression. Gene expression needs to be transcribed from DNA to RNA, translated into protein, and modified into mature protein to perform biological functions. This figure highlights the influence of RBPs, microRNAs, lncRNAs, circRNAs, and RNA m6A modification on the protein translation procedure in tumorigenesis
Fig. 2
Fig. 2
The model of protein translation process. Translation is initiated by eIF4F assembly, consists of eIF4A, eIF4E, and eIF4G. The hypophosphorylated form of 4E-BPs competes with eIF4G to bind eIF4E, and phosphorylated eIF2α fails to recover the GTP required for Met-tRNAi, resulting in failure of the formation of eIF4F complexes and inhibits translation. Extension: the initiation complex of cap-dependent translation scans the mRNA from the 5 ‘end to find the first start codon (AUG), and enters the ribosomal P-site via initiator methionyl tRNA (Met-tRNAi). Termination: when the mRNA with stop codon (UAG, UGA, UAA) enters the ribosomal A-site, it can’t be recognized by activated amino acid (aa-tRNA), the translation process is finished
Fig. 3
Fig. 3
m6A modification regulates protein translation. The m6A modification is catalyzed by the writers (METTL3/METTL14/WTAP, WETTL16) and demethylated by erasers (FTO, ALKBH5). The m6A modification is recognized by the readers (YTHDF1/2/3, YTHDC1/2, IGF2BP1/2/3, and HuR). The translation procedure of target genes can be influenced by the m6A modification level
See this image and copyright information in PMC

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