Synonymous mutations that regulate translation speed might play a non-negligible role in liver cancer development

Abstract

Background Synonymous mutations do not change the protein sequences. Automatically, they have been regarded as neutral events and are ignored in the mutation-based cancer studies. However, synonymous mutations will change the codon optimality, resulting in altered translational velocity. Methods We fully utilized the transcriptome and translatome of liver cancer and normal tissue from ten patients. We profiled the mutation spectrum and examined the effect of synonymous mutations on translational velocity. Results Synonymous mutations that increase the codon optimality significantly enhanced the translational velocity, and were enriched in oncogenes. Meanwhile, synonymous mutations decreasing codon optimality slowed down translation, and were enriched in tumor suppressor genes. These synonymous mutations significantly contributed to the translational changes in tumor samples compared to normal samples. Conclusions Synonymous mutations might play a role in liver cancer development by altering codon optimality and translational velocity. Synonymous mutations should no longer be ignored in the genome-wide studies.

SARS-CoV-2 competes with host mRNAs for efficient translation by maintaining the mutations favorable for translation initiation

“…Affecting the RNA structure is only one feature of a mutation (Chamary and Hurst 2005 ). Codon usage bias is a typical feature that could affect mRNA translation rate so that the mutations in CDS that alter the codon usage could consequently affect translation (Li et al 2021 ). Apart from the translation issue, the mutations in CDS could change amino acids and have more profound effects on the fitness of viral sequence (Becerra-Flores and Cardozo 2020 ).…”

“…Regarding the translation process, our article only discusses translation initiation. What is also important is translation elongation, the speed of which is largely dependent on the codon composition (Li et al 2021 ; Taghinezhad et al 2017 ). Codon composition is again tightly connected to mutations in CDS.…”

“…Among the numerous biological processes, RNA translation is believed to be the most energy-consuming and rate-limiting step (Li et al 2021 ; Zhao et al 2021 ). For SARS-CoV-2, a successful invasion is measured by how many viral particles are produced, rather than how many viral RNAs are replicated.…”

RNA editing detection in SARS-CoV-2 transcriptome should be different from traditional SNV identification

“…The identification of single-nucleotide variant (SNV) is a basic bioinformatic skill in nearly all the genome-wide mutation analyses and comparative genomics studies (Jiang et al 2021 ; Jiang et al 2022 ; Li et al 2021 ). For example, in the 1000-genome project (Kuehn 2008 ), the ultimate goal of the SNP (single-nucleotide polymorphism)-calling step is to find out the difference between the reference genome and the genome of a given individual.…”

Genome-wide expression changes mediated by A-to-I RNA editing correlate with hepatic oncogenesis

“…However, when one talks about gene expression, what is the definition of “a gene”? One gene has different isoforms (transcripts), translation start and stop sites ( 27 , 28 ), allele-specific expression caused by mutations ( 29 , 30 ), and one isoform could have different combinations of RNA editing events, and these molecules are actually different alleles (with potentially different functions), but they are usually pooled and regarded as the same “gene.” The automatic omission of RNA editing information is arbitrary and may miss important clues. For example, it has been reported that A-to-I editing-mediated isoform switches could lead to leukemia ( 31 ).…”