MOLECULAR MECHANISMS OF CALCITONIN GENE TRANSCRIPTION AND POST-TRANSCRIPTIONAL RNA PROCESSING

Publisher Summary This chapter discusses the molecular mechanisms of calcitonin (CT) gene transcription and posttranscriptional RNA processing. The primary site of CT production in mammals is the parafollicular cell or C cell of the thyroid gland. This cell type originates in the neural crest and migrates, during embryonic life, to the fourth pharyngeal pouch. A mass of the C-cell precursors, collectively known as the ultimobranchial body, fuses with the thyroid gland as it migrates caudally during neck morphogenesis. Transcription of protein-encoding genes by eukaryotic RNA polymerase II is regulated by interaction of trans -acting factors with specific DNA sequences, cis elements. The cell-restricted transcription of a gene is mediated by one or a combination of cis elements that function to enhance or repress transcription. The removal of intronic sequence between adjacent exons occurs in two steps. Exon sequence is first defined by recognition processing signals and then splicing proceeds by removal of sequence between defined exons These elements are located in regions flanking the transcription unit or within the transcription unit itself. The key event in the processing of the CT pre-mRNA is the inclusion or exclusion of exon four.