mRNA的3'非翻譯區(qū)（3'UTR）作為mRNA的一部分,，其調(diào)控自身mRNA的功能已為人們所熟知,。但對(duì)于脫離mRNA而單獨(dú)存在于細(xì)胞內(nèi)的3'UTR(獨(dú)立3'UTR RNA), 直到最近還很少被研究，甚至其是否存在也有爭(zhēng)議,。

CCAAT/增強(qiáng)子結(jié)合蛋白β（C/EBPβ,，又叫NF-IL6） 3'UTR是上海生科院生化與細(xì)胞所劉定干研究組首先（1991）發(fā)現(xiàn)的一個(gè)有功能的獨(dú)立3'UTR RNA。它具有使惡性細(xì)胞的惡性程度降低（逆轉(zhuǎn)）的功能,，即腫瘤抑制功能,。最近該組發(fā)現(xiàn)，C/EBPβ 3'UTR RNA是通過(guò)與惡性細(xì)胞內(nèi)的癌基因----蛋白激酶（PK）Cε相互作用,，抑制其磷酸化活力而實(shí)現(xiàn)腫瘤抑制的,。這一成果發(fā)表在2011年1月24日的PLoS ONE上。

劉定干研究組的博士研究生王瑩等發(fā)現(xiàn),，C/EBPβ 3'UTR RNA在細(xì)胞內(nèi)能與細(xì)胞角蛋白18結(jié)合,，改變其細(xì)胞內(nèi)組織，并影響細(xì)胞周期的進(jìn)程,；在所研究的惡性細(xì)胞中,，主要起作用的蛋白激酶是PKCε，在逆轉(zhuǎn)細(xì)胞中活力降低的也是PKCε; 使PKCε抑制的則是C/EBPβ 3'UTR RNA,。在體外實(shí)驗(yàn)中,，C/EBPβ 3'UTR RNA能抑制PKCε的活力；在細(xì)胞內(nèi),，C/EBPβ 3'UTR RNA通過(guò)與PKCε和細(xì)胞角蛋白18三者形成復(fù)合物,，使PKCε對(duì)其靶蛋白的磷酸化活力被抑制，因此導(dǎo)致細(xì)胞惡性度降低,。

該項(xiàng)研究工作得到國(guó)家自然科學(xué)基金資助。（生物谷Bioon.com）

生物谷推薦原文出處：

PLoS ONE 6(1): e16543. doi:10.1371/journal.pone.0016543

Tumor Suppression by RNA from C/EBPβ 3′UTR through the Inhibition of Protein Kinase Cε Activity

Ying Wang, Da-Quan Sun, Ding-Gan Liu*

Abstract

Background

Since the end of last century, RNAs from the 3′untranslated region (3′UTR) of several eukaryotic mRNAs have been found to exert tumor suppression activity when introduced into malignant cells independent of their whole mRNAs. In this study, we sought to determine the molecular mechanism of the tumor suppression activity of a short RNA from 3′UTR of C/EBPβ mRΝΑ (C/EBPβ 3′UTR RNA) in human hepatocarcinoma cells SMMC-7721.

Methodology/Principal Findings

By using Western blotting, immunocytochemistry, molecular beacon, confocal microscopy, protein kinase inhibitors and in vitro kinase assays, we found that, in the C/EBPβ 3′UTR-transfectant cells of SMMC-7721, the overexpressed C/EBPβ 3′UTR RNA induced reorganization of keratin 18 by binding to this keratin; that the C/EBPβ 3′UTR RNA also reduced phosphorylation and expression of keratin 18; and that the enzyme responsible for phosphorylating keratin 18 is protein kinase Cε. We then found that the C/EBPβ 3′UTR RNA directly inhibited the phosphorylating activity of protein kinase Cε; and that C/EBPβ 3′UTR RNA specifically bound with the protein kinase Cε-keratin 18 conjugate.

Conclusion/Significance

Together, these facts suggest that the tumor suppression in SMMC-7721 by C/EBPβ 3′UTR RNA is due to the inhibition of protein kinase Cε activity through direct physical interaction between C/EBPβ 3′UTR RNA and protein kinase Cε. These facts indicate that the 3′UTR of some eukaryotic mRNAs may function as regulators for genes other than their own.