Regulation of Alternative RNA Processing of the Human Calcitonin/CGRP Gene

Case Western Reserve University, Cleveland OH

Investigators

Abstract

Alternative RNA processing is a process that generates multiple protein isoforms from a single gene, and thus is an important regulator of gene expression. Up to 60% of human pre-mRNAs undergo alternative processing, making this a ubiquitous biological process. The long-term goal of this research is to understand the mechanism that controls tissue-specific alternative RNA processing using the human calcitonin/calcitonin gene-related peptide (CGRP) gene as a model. The calcitonin/CGRP pre-mRNA is processed to produce calcitonin in thyroid cells and CGRP in neurons. Previous studies have identified an intron element and several splicing factors that are required for calcitonin production. Very little is known about the neuron-specific CGRP-producing pathway. Recent studies from the PI's laboratory have identified two additional factors TIA and a neuron-specific factor. These new factors suggest a novel role of the intron element in addition to previously characterized polyadenylation enhancement function. The goal of this project is to characterize this novel role of the intronic element and determine the precise functions of TIA and the neuronal factor in regulated processing of the calcitonin/CGRP pre-mRNA. The combined data from these studies will provide fundamental insights into regulated RNA processing. Moreover, these studies on the neuron-specific factor will significantly advance knowledge of tissue-specific control of alternative splicing.