TISSUE-SPECIFIC ALTERNATIVE RNA PROCESSING IN CALCITONIN CALCITONIN-GENE-RELATED PEPTIDE GENE-EXPRESSION

The alternative splicing of messenger RNA (mRNA) precursors represents a common mechanism for increasing the flexibility of eukaryotic gene expression by the generation of structurally distinct, developmentally regulated and tissue-specific protein isoforms. The calcitonin/calcit onin-gene-related peptide (CGRP) primary RNA transcript undergoes tiss ue-specific alternative processing, resulting in the differential prod uction of calcitonin mRNA in thyroid C cells and CGRP mRNA in neurons of the central and peripheral nervous systems. The calcitonin/CGRP gen e provides an excellent model for examining the regulation of cell-spe cific alternative RNA processing events in complex transcription units expressed within the neuroendocrine system. Initial studies attemptin g to delineate the biochemical events involved in the regulation of th ese cellular processes have taken advantage of a number of molecular b iological techniques including expression of the calcitonin/CGRP trans cription unit in transgenic mice, tissue culture model systems that mi mic the alternative RNA processing choices made by tissues in vivo and the development of in vitro splicing systems. It is anticipated that combinations of these experimental approaches will allow the definitio n of biochemical processes and the isolation of the cellular machinery involved in the regulation of cell-specific RNA processing events.