7 - RNA processing regulation and interindividual variation

Summary

OVERVIEW

In the search for causes of human disease and variability of drug response, the study of inter-individual differences in RNA processing has lagged substantially behind analyses at the DNA level. The processes of RNA editing and RNA splicing represent important mechanisms that ultimately contribute to the expression of specific protein isoforms within a given cell. Moreover, these events are subject to complex regulation that differs with each cell's make-up, permitting intricate regulation of the cellular protein repertoire. This review will focus upon the post-transcriptional processes of RNA editing and alternative splicing and consider the contribution of aberrations within these events to the efficacy of pharmacotherapy for psychiatric diseases. Specific examples of RNA processing defects within receptors for various neurotransmitters such as dopamine, glutamate, and serotonin will be presented. In addition, mechanisms involved in the regulation of RNA editing and splicing will be addressed as contributors to disease etiology and treatment. It is anticipated that studies of RNA processing regulation will enhance our understanding of disease pathology and eventually improve the rational design of therapeutic compounds.

Introduction

The sequencing of the human genome will almost certainly unlock the secrets of a multitude of human diseases. For the first time, both exonic and intronic regions of the genetic code will be available for analyses of potential disease-causing mutations. For disorders such as depression and schizophrenia, the identification of individual genetic variability will almost certainly provide information as to their etiology and treatment.