Messenger RNA processing and its role in diabetes

Abstract

The past few years have seen huge advances in our understanding of the genetics of diabetes. However, definition of the mechanisms that underpin these observations is less clear. It is now becoming apparent that the processes that mediate these effects are complex and interlinked, and will require consideration of other factors in addition to the DNA sequence. The information in our genes is conveyed to the cellular machinery via an intermediate molecule, RNA. However, we now understand that RNA is not merely a messenger, as RNA-based mechanisms are responsible for a large proportion of the fine-tuning of gene expression and gene regulation. The initial RNA transcript produced undergoes a series of modifications known as RNA processing to generate a mature messenger RNA (mRNA). This includes addition of the 5' cap sequences and the poly-A tail of the mRNA molecule, and removal of its intronic sequences. The exact pattern of mRNA processing may vary from cell type to cell type and differ in response to internal and external stimuli. In this review, using examples from my own work, I will outline how mRNA processing mechanisms can sometimes provide a mode of action for mutations causing monogenic diabetes, and also suggest potential explanations for phenotypic variation in this condition. The potential for mRNA processing to impact on more complex causes of diabetes as well will also be considered.