title: Decoding mechanisms by which silent codon changes influence protein biogenesis and function.
abstract: METHODS
  Synonymous codon usage has been a focus of investigation since the discovery of the genetic code and its redundancy. The occurrences of synonymous codons vary between species and within genes of the same genome, known as codon usage bias. Today, bioinformatics and experimental data allow us to compose a global view of the mechanisms by which the redundancy of the genetic code contributes to the complexity of biological systems from affecting survival in prokaryotes, to fine tuning the structure and function of proteins in higher eukaryotes. Studies analyzing the consequences of synonymous codon changes in different organisms have revealed that they impact nucleic acid stability, protein levels, structure and function without altering amino acid sequence. As such, synonymous mutations inevitably contribute to the pathogenesis of complex human diseases. Yet, fundamental questions remain unresolved regarding the impact of silent mutations in human disorders. In the present review we describe developments in this area concentrating on mechanisms by which synonymous mutations may affect protein function and human health.
  
  
  OBJECTIVE
  This synopsis illustrates the significance of synonymous mutations in disease pathogenesis. We review the different steps of gene expression affected by silent mutations, and assess the benefits and possible harmful effects of codon optimization applied in the development of therapeutic biologics.
  Understanding mechanisms by which synonymous mutations contribute to complex diseases such as cancer, neurodegeneration and genetic disorders, including the limitations of codon-optimized biologics, provides insight concerning interpretation of silent variants and future molecular therapies.
authors: Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors: Vedrana
authors: V
authors: Bali
authors: Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address: bebok@uab.edu.
authors: Zsuzsanna
authors: Z
authors: Bebok
mesh_terms: D000818:Animals; D001483:Base Sequence; D003062:Codon; D019143:Evolution, Molecular; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D014176:Protein Biosynthesis; D017510:Protein Folding; D059370:RNA Folding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000502:physiology
chemical_list: D003062:Codon; D012333:RNA, Messenger
keywords: Codon usage bias (CUB); Protein folding; Translation dynamics; mRNA structure; sSNP