Lescure Alain, Allmang Christine, Yamada Kenichiro, Carbon Philippe, Krol Alain
UPR 9002 du Centre National de la Recherche Scientifique, Institut de Biologie Moléculaire et Cellulaire, 15, Rue René Descartes, 67084 Strasbourg Cedex, France.
Gene. 2002 May 29;291(1-2):279-85. doi: 10.1016/s0378-1119(02)00629-7.
Selenocysteine and selenoprotein synthesis require a complex molecular machinery in mammals. Among the key players is the RNA-protein complex formed by the selenocysteine insertion sequence (SECIS) binding protein (SBP2) and the SECIS element, an RNA hairpin in the 3' untranslated regions of selenoprotein messenger RNAs (mRNAs). We have isolated the DNA complementary to mRNA of the human SBP2, enabling us to establish that it differs from a previously reported human SBP2-like protein. Examination of the expression pattern revealed that the human SBP2 protein is encoded by a 4 kb long mRNA that is over-expressed in testis. Compared to the rat SBP2 sequence, the human SBP2 protein displays two highly conserved domains with 92 and 95% amino acid identity, the latter one containing the RNA binding domain. The inter-domain section carries 55% sequence identity, the remainder of the SBP2 sequences showing about 65% identity, values lower than expected for two mammalian proteins. Interestingly, we could show that the binding of human SBP2 to the SECIS RNA is stimulated by the selenoprotein-specialized elongation translation factor mSelB/eEFsec.
在哺乳动物中,硒代半胱氨酸和硒蛋白的合成需要复杂的分子机制。其中的关键成分是由硒代半胱氨酸插入序列(SECIS)结合蛋白(SBP2)和SECIS元件形成的RNA-蛋白质复合物,SECIS元件是硒蛋白信使核糖核酸(mRNA)3'非翻译区中的一个RNA发夹结构。我们分离出了与人类SBP2的mRNA互补的DNA,这使我们能够确定它与之前报道的一种人类SBP2样蛋白不同。对表达模式的研究表明,人类SBP2蛋白由一个4 kb长的mRNA编码,该mRNA在睾丸中过度表达。与大鼠SBP2序列相比,人类SBP2蛋白有两个高度保守的结构域,氨基酸同一性分别为92%和95%,后者包含RNA结合结构域。结构域间区域的序列同一性为55%,SBP2序列的其余部分显示约65%的同一性,这一数值低于两种哺乳动物蛋白的预期值。有趣的是,我们能够证明硒蛋白特异性延伸翻译因子mSelB/eEFsec可刺激人类SBP2与SECIS RNA的结合。