Alternative RNA Splicing of Calcitonin/Calcitonin Gene-Related Peptide Minigene Transcripts in a Thyroid C-Cell Line

RNA transcripts derived from the calcitonin (CT)/calcitonin gene-related peptide (CGRP) gene are differentially processed in a tissue-specific fashion to produce two unique mRNAs. This RNA processing decision is deregulated in malignant thyroid C-cells. To examine this mechanism of RNA processing, CT/CGRP minigene constructs were transfected into the human medullary thyroid carcinoma TT cell line. RNA derived from the normal CT/CGRP construct paralleled the endogeneous pathway to produce both CT and CGRP mRNAs. Mutation analysis and RNA/protein crosslinking were performed in order to clarify trans-acting factor interactions. The data suggest that CGRP production in TT cells results from the coexpression of facilitative and inhibitory factors.