Splice commitment dictates neuron-specific alternative RNA processing in calcitonin/CGRP gene expression.
The calcitonin/CGRP gene is a complex transcription unit in which developmentally regulated cell-specific alternative RNA processing results in the production of CGRP mRNA in neurons, and of calcitonin mRNA in thyroid C cells. Alternative poly(A) site selection and exon splicing lead to the production of these alternative mature transcripts. The wild-type and a series of mutated calcitonin/CGRP genes were expressed in heterologous cell types, which produced predominantly calcitonin or CGRP mRNA. The results of these studies suggest that neurons express machinery or a factor that determines a specific alternative splicing pathway and consequently its associated alternative poly(A) site selection. It is hypothesized that a splice commitment regulatory factor might modulate pre-mRNA secondary structure, revealing a cryptic splice site required to generate CGRP mRNA in the brain.
D000818:Animals; D002116:Calcitonin / Q000235:genetics*; D015740:Calcitonin Gene-Related Peptide; D002460:Cell Line; D005796:Genes; D007438:Introns; D008957:Models, Genetic; D009154:Mutation; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics*; D011061:Poly A / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
D009479:Neuropeptides; D012333:RNA, Messenger; D011061:Poly A; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide