Hoshino S, Hosoda N, Araki Y, Kobayashi T, Uchida N, Funakoshi Y, Katada T
Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, 113-0033, Japan.
Biochemistry (Mosc). 1999 Dec;64(12):1367-72.
The mammalian GTP-binding protein GSPT, whose carboxy-terminal sequence is homologous to the eukaryotic elongation factor EF1alpha, binds to the polypeptide chain releasing factor eRF1 to function as eRF3 in translation termination. However, the amino-terminal domain of GSPT, which contains a prion-like sequence, is not required for the binding. Instead, the amino-terminal domain is capable of binding to the carboxy-terminal domain of polyadenylate-binding protein (PABP), whose amino terminus is associating with the poly(A) tail of mRNAs, presumably for their stabilization. Interestingly, multimerization of PABP with poly(A), which is ascribed to the action of its carboxy-terminal domain, was completely inhibited by the interaction with the amino-terminal domain of GSPT. This may facilitate shortening of the poly(A) tail of mRNAs by an RNase. Thus, GSPT/eRF3 appears to function not only as a stimulator of eRF1 in the translation termination but also as an initiator of the mRNA degradation machinery. Further physiological and cell biological approaches will be necessary to show whether our current in vitro findings on GSPT/eRF3 indeed reflect its bifunctional properties in living cells.
哺乳动物的GTP结合蛋白GSPT，其羧基末端序列与真核延伸因子EF1α同源，在翻译终止过程中与多肽链释放因子eRF1结合，作为eRF3发挥作用。然而，GSPT的氨基末端结构域（包含一个类朊病毒序列）并非结合所必需。相反，氨基末端结构域能够与聚腺苷酸结合蛋白（PABP）的羧基末端结构域结合，PABP的氨基末端与mRNA的聚（A）尾相关联，推测是为了使其稳定。有趣的是，PABP与聚（A）的多聚化（归因于其羧基末端结构域的作用）被与GSPT氨基末端结构域的相互作用完全抑制。这可能有助于核糖核酸酶缩短mRNA的聚（A）尾。因此，GSPT/eRF3似乎不仅在翻译终止中作为eRF1的刺激因子发挥作用，还作为mRNA降解机制的启动因子。需要进一步的生理学和细胞生物学方法来证明我们目前关于GSPT/eRF3的体外研究结果是否确实反映了其在活细胞中的双功能特性。
