Pathological Variations in 3′‐Untranslated Regions of Human Genes

Abstract

Abstract The 3′‐untranslated regions (UTRs) of messenger ribonucleic acids (mRNAs) play a critical role in the stabilisation, localisation and translation of mRNAs. Mutations that disrupt functional elements of the 3′‐UTR of mRNAs such as polyadenylation signal, microribonucleic acid (miRNA) target sites and AU‐rich elements lead to production of nonfunctional proteins or reduced amounts of functional proteins. Genetic variations in the 3′‐UTR are associated with disease risk or diseases such as spinocerebellar ataxia 8, Parkinson disease, breast cancer, atopic dermatitis, papillary thyroid carcinoma and many others. With the advent of genetic counselling and promise of personalised medicine, genetic variation in this region of mRNAs is the focus of intense research. Current research shows that this region is of immense significance in the context of translational research. Key Concepts 3′‐Untranslated regions (UTRs) are noncoding regions of mRNAs. The 3′‐UTR is delimited by stop codon (UAA or UAG or UGA) at the 5′‐end and poly (A) tail at the 3′‐end. Motifs such as AU‐rich elements, polyadenylation signal, iron responsive elements and others are involved in mRNA stability, localisation and translation. Mutations are changes in the DNA/gene of an organism which are heritable. Mutations in the AU‐rich elements lead to atypical stabilisation of mRNA and associated diseases. Mutations that lead to abolition of canonical polyadenylation signal interfere with efficient transcription termination and polyadenylation of mRNA. Mutations in the 3′‐UTR may alter the binding sites of interacting miRNAs or proteins resulting in deregulation of mRNA translation. Single‐nucleotide polymorphisms (SNPs) in the 3′‐UTR are associated with individual's drug response and disease risk.