Leff S E, Evans R M, Rosenfeld M G
Cell. 1987 Feb 13;48(3):517-24. doi: 10.1016/0092-8674(87)90202-9.
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.
降钙素/CGRP基因是一个复杂的转录单位，其中发育调控的细胞特异性可变RNA加工导致在神经元中产生CGRP mRNA，在甲状腺C细胞中产生降钙素mRNA。可变聚腺苷酸化位点选择和外显子剪接导致这些可变成熟转录本的产生。野生型和一系列突变的降钙素/CGRP基因在异源细胞类型中表达，这些细胞类型主要产生降钙素或CGRP mRNA。这些研究结果表明，神经元表达决定特定可变剪接途径及其相关可变聚腺苷酸化位点选择的机制或因子。据推测，一种剪接决定调节因子可能调节前体mRNA二级结构，揭示在大脑中产生CGRP mRNA所需的隐蔽剪接位点。
