To serve as templates for translation eukaryotic mRNAs undergo an elaborate processing and maturation pathway. In eukaryotes this process comprises the synthesis of mRNA precursors, their processing and transport to the site of translation and eventually their decay. During the entire life cycle, mRNAs interact with distinct sets of trans-acting factors that determine their fate at any given phase of gene expression. Recent studies have shown that mutations in components acting in trans on mRNAs are frequent causes of a large variety of different human disorders. The etiology of most of these diseases is, however, only poorly understood, mostly because the consequences for mRNA-metabolism are unclear. Here we discuss three prominent genetic diseases that fall into this category, namely spinal muscular atrophy (SMA), retinitis pigmentosa (RP) and X-linked syndromic mental retardation (XLMR). Whereas SMA and RP can be directly linked to mRNA processing, XLMR results from mutations in the mRNA surveillance system. We discuss how defects in mRNA maturation and turnover might lead to the tissue specific defects seen in these diseases.
Keywords: Genetic disease; Post-transcriptional regulation of gene expression; Splicing; mRNA; mRNA turnover.
Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.