Mutations in cis that affect mRNA synthesis, processing and translation

• Published in: Biochimica et biophysica acta. Molecular basis of disease 2021-09, Vol.1867 (9), p.166166-166166, Article 166166
• Main Authors: Roos, Dirk, de Boer, Martin
• Format: Article
• Language: English
• Subjects: Kozak sequence; Micro-RNA; mRNA processing; Non-coding RNA; Pre-mRNA methylation; Pre-mRNA splicing; RNA-binding proteins; SR proteins; Transcription factors
• ISSN: 0925-4439; 1879-260X
• DOI: 10.1016/j.bbadis.2021.166166

Genetic mutations that cause hereditary diseases usually affect the composition of the transcribed mRNA and its encoded protein, leading to instability of the mRNA and/or the protein. Sometimes, however, such mutations affect the synthesis, the processing or the translation of the mRNA, with similar disastrous effects. We here present an overview of mRNA synthesis, its posttranscriptional modification and its translation into protein. We then indicate which elements in these processes are known to be affected by pathogenic mutations, but we restrict our review to mutations in cis, in the DNA of the gene that encodes the affected protein. These mutations can be in enhancer or promoter regions of the gene, which act as binding sites for transcription factors involved in pre-mRNA synthesis. We also describe mutations in polyadenylation sequences and in splice site regions, exonic and intronic, involved in intron removal. Finally, we include mutations in the Kozak sequence in mRNA, which is involved in protein synthesis. We provide examples of genetic diseases caused by mutations in these DNA regions and refer to databases to help identify these regions. The over-all knowledge of mRNA synthesis, processing and translation is essential for improvement of the diagnosis of patients with genetic diseases. •Mutations in protein-coding genes usually affect mRNA composition.•However, they can also affect mRNA synthesis, processing or translation.•Mutations in transcription factor-binding sites can diminish mRNA synthesis.•Mutations in polyadenylation or splice sites can hamper correct mRNA processing.•Mutations in the Kozak sequence can diminish mRNA translation into protein.