Epstein E, Sela-Brown A, Ringel I, Kilav R, King S M, Benashski S E, Yisraeli J K, Silver J, Naveh-Many T
Minerva Center for Calcium and Bone Metabolism, Nephrology Services, Hadassah University Hospital, Jerusalem, Israel 91120.
J Clin Invest. 2000 Feb;105(4):505-12. doi: 10.1172/JCI8557.
The 3'-untranslated region (UTR) of mRNAs binds proteins that determine mRNA stability and localization. The 3'-UTR of parathyroid hormone (PTH) mRNA specifically binds cytoplasmic proteins. We screened an expression library for proteins that bind the PTH mRNA 3'-UTR, and the sequence of 1 clone was identical to that of the dynein light chain LC8, a component of the dynein complexes that translocate cytoplasmic components along microtubules. Recombinant LC8 binds PTH mRNA 3'-UTR, as shown by RNA electrophoretic mobility shift assay. We showed that PTH mRNA colocalizes with microtubules in the parathyroid gland, as well as with a purified microtubule preparation from calf brain, and that this association was mediated by LC8. To our knowledge, this is the first report of a dynein complex protein binding an mRNA. The dynein complex may be the motor that is responsible for transporting mRNAs to specific locations in the cytoplasm and for the consequent is asymmetric distribution of translated proteins in the cell.
mRNA的3'非翻译区(UTR)可结合决定mRNA稳定性和定位的蛋白质。甲状旁腺激素(PTH)mRNA的3'-UTR特异性结合细胞质蛋白。我们筛选了一个表达文库,寻找能结合PTH mRNA 3'-UTR的蛋白质,其中1个克隆的序列与动力蛋白轻链LC8相同,动力蛋白轻链LC8是动力蛋白复合体的一个组成部分,可沿微管转运细胞质成分。如RNA电泳迁移率变动分析所示,重组LC8可结合PTH mRNA 3'-UTR。我们发现,PTH mRNA在甲状旁腺中与微管共定位,在来自小牛脑的纯化微管制剂中也与微管共定位,且这种结合是由LC8介导的。据我们所知,这是关于动力蛋白复合体蛋白结合mRNA的首次报道。动力蛋白复合体可能是负责将mRNA转运至细胞质中特定位置以及导致细胞内翻译蛋白不对称分布的“发动机”。