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异质性核糖核蛋白C通过稳定淀粉样前体蛋白（APP）的信使核糖核酸来增加其产量。

hnRNP C increases amyloid precursor protein (APP) production by stabilizing APP mRNA.

作者信息

Rajagopalan L E, Westmark C J, Jarzembowski J A, Malter J S

机构信息

Neuroscience Program, Institute on Aging and Department of Pathology and Laboratory Medicine,University of Wisconsin-Medical School, Madison, WI 53792, USA.

出版信息

Nucleic Acids Res. 1998 Jul 15;26(14):3418-23. doi: 10.1093/nar/26.14.3418.

DOI:10.1093/nar/26.14.3418
PMID:9649628
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC147701/
Abstract

We have previously shown that heterogeneous nuclear ribonucleoprotein C (hnRNP C) and nucleolin bound specifically to a 29 nt sequence in the 3'-untranslated region of amyloid precursor protein (APP) mRNA. Upon activation of peripheral blood mononuclear cells, hnRNP C and nucleolin acquired APP mRNA binding activity, concurrent with APP mRNA stabilization. These data suggested that the regulated interaction of hnRNP C and nucleolin with APP mRNA controlled its stability. Here we have directly examined the role of the cis element and trans factors in the turnover and translation of APP mRNA in vitro . In a rabbit reticulocyte lysate (RRL) translation system, a mutant APP mRNA lacking the 29 nt element was 3-4-fold more stable and synthesized 2-4-fold more APP as wild-type APP mRNA. Therefore, the 29 nt element functioned as an APP mRNA destabilizer. RNA gel mobility shift assays with the RRL suggested the presence of endogenous nucleolin, but failed to show hnRNP C binding activity. However, wild-type APP mRNA was stabilized and coded for 6-fold more APP when translated in an RRL system supplemented with exogenous active hnRNP C. Control mRNAs lacking the 29 nt element were unaffected by hnRNP C supplementation. Therefore, occupancy of the 29 nt element by hnRNP C stabilized APP mRNA and enhanced its translation.

摘要

我们之前已经表明，异质性核核糖核蛋白C（hnRNP C）和核仁素特异性结合淀粉样前体蛋白（APP）mRNA 3'-非翻译区的一段29个核苷酸的序列。在外周血单核细胞激活后，hnRNP C和核仁素获得APP mRNA结合活性，同时APP mRNA稳定性增加。这些数据表明，hnRNP C和核仁素与APP mRNA的调控相互作用控制了其稳定性。在此，我们直接研究了顺式元件和反式因子在体外APP mRNA周转和翻译中的作用。在兔网织红细胞裂解物（RRL）翻译系统中，缺少29个核苷酸元件的突变型APP mRNA的稳定性比野生型APP mRNA高3-4倍，合成的APP比野生型多2-4倍。因此，29个核苷酸元件起到APP mRNA不稳定因子的作用。用RRL进行的RNA凝胶迁移率变动分析表明存在内源性核仁素，但未显示hnRNP C结合活性。然而，当在补充有外源性活性hnRNP C的RRL系统中进行翻译时，野生型APP mRNA的稳定性增加，编码的APP增加6倍。缺少29个核苷酸元件的对照mRNA不受hnRNP C补充的影响。因此，hnRNP C占据29个核苷酸元件可使APP mRNA稳定并增强其翻译。