Identification of mRNAs under translational control by Fhit

Fhit is a tumor suppressor/genomic protective protein that is lost in more than 50% of cancers but the mechanism by which it works is unknown. Unlike most tumor suppressors Fhit is a cytoplasmic protein with no known interacting partners. A previous study found that Fhit regulates the translation of thymidine kinase 1 (TK1) mRNA into protein, with greater TK1 translation in Fhit-positive versus Fhit-negative cells. Increased TK1 translation was dependent on the ability of Fhit to degrade small RNA fragments termed nucleoside 5',5'-triphosphates. The goal of this study was to identify mRNAs whose translation is regulated by Fhit, and use this information to identify the proteins that are responsible for its tumor suppressor/genome protective effects.Fhit是一种肿瘤抑制/基因组保护蛋白，在超过50%的癌症中发生缺失，但其发挥作用的分子机制尚不明确。与多数肿瘤抑制因子不同，Fhit属于细胞质蛋白，目前尚未发现其已知的相互作用蛋白。既往一项研究发现，Fhit可调控胸苷激酶1（thymidine kinase 1, TK1）的信使核糖核酸（messenger RNA, mRNA）翻译为蛋白质的过程，且Fhit阳性细胞中的TK1翻译水平高于Fhit阴性细胞。TK1翻译水平的提升依赖于Fhit降解被称为核苷5',5'-三磷酸的小RNA片段的能力。本研究旨在鉴定受Fhit调控翻译过程的mRNA，并以此为依据解析介导其肿瘤抑制与基因组保护功能的核心蛋白。