Lacaze-Masmonteil T, de Keyzer Y, Luton J P, Kahn A, Bertagna X
Institut National de la Santé et de la Recherche Medicale Unité U-129, Hôpital Cochin, Paris, France.
Proc Natl Acad Sci U S A. 1987 Oct;84(20):7261-5. doi: 10.1073/pnas.84.20.7261.
Proopiomelanocortin (POMC), the precursor to adrenocorticotropic hormone and other related peptides, was originally identified in the corticotropic cell. Recent evidence shows that POMC products are also normally present in a variety of nonpituitary tissues. To investigate this phenomenon in humans we looked for the presence and characteristics of POMC transcripts in various adult tissues. Blot hybridization analysis of normal adrenal, thymus, and testis RNAs revealed a small RNA species approximately 400 nucleotides shorter than the 1200-nucleotide pituitary species. Primer extension and S1 nuclease mapping studies showed that this small RNA lacked exon 1 and exon 2 of the gene, and it corresponded to a set of at least six molecules starting 41 to 162 nucleotides downstream from the 5' end of exon 3. These RNAs appear to result from heterogeneous transcription initiation sites presumably under the control of "GC box" promoter sequences located in the 3' end of intron 2. They cannot encode a complete POMC molecule, and the only truncated POMC molecules that could be translated would lack a signal peptide necessary for membrane translocation and precursor processing. The use of highly sensitive S1 nuclease mapping techniques with uniformly labeled single-stranded DNA probes allowed the detection of a small but definite amount of the "normal," 1200-nucleotide, mRNA species. It is suggested that it is this POMC mRNA that is responsible for the local production of all the POMC peptides.
促肾上腺皮质激素原（POMC）是促肾上腺皮质激素及其他相关肽的前体，最初是在促肾上腺皮质激素细胞中发现的。最近的证据表明，POMC产物在多种非垂体组织中也正常存在。为了在人类中研究这一现象，我们探寻了各种成人组织中POMC转录本的存在情况及特征。对正常肾上腺、胸腺和睾丸RNA进行印迹杂交分析，发现一种小RNA分子，其长度比垂体中的1200个核苷酸的RNA分子短约400个核苷酸。引物延伸和S1核酸酶图谱分析研究表明，这种小RNA缺少该基因的外显子1和外显子2，它对应于一组至少六个分子，这些分子从外显子3 5'端下游41至162个核苷酸处起始。这些RNA似乎源于异质性转录起始位点，推测受位于内含子2 3'端的“GC框”启动子序列控制。它们无法编码完整的POMC分子，唯一可能被翻译的截短POMC分子将缺少膜转运和前体加工所需的信号肽。使用高度敏感的S1核酸酶图谱技术和均匀标记的单链DNA探针，能够检测到少量但确定数量 的“正常” 的1200个核苷酸的mRNA分子。有人提出，正是这种POMC mRNA负责所有POMC肽的局部产生。
