mRNA的3'非翻译区（3'UTR）作为mRNA的一部分，其调控自身mRNA的功能已为人们所熟知。但对于脱离mRNA而单独存在于细胞内的3'UTR(独立3'UTR RNA), 直到最近还很少被研究，甚至其是否存在也有争议。
CCAAT/增强子结合蛋白β（C/EBPβ，又叫NF-IL6） 3'UTR是上海生科院生化与细胞所刘定干研究组首先（1991）发现的一个有功能的独立3'UTR RNA。它具有使恶性细胞的恶性程度降低（逆转）的功能，即肿瘤抑制功能。最近该组发现，C/EBPβ 3'UTR RNA是通过与恶性细胞内的癌基因----蛋白激酶（PK）Cε相互作用，抑制其磷酸化活力而实现肿瘤抑制的。这一成果发表在2011年1月24日的PLoS ONE上。
刘定干研究组的博士研究生王莹等发现，C/EBPβ 3'UTR RNA在细胞内能与细胞角蛋白18结合，改变其细胞内组织，并影响细胞周期的进程；在所研究的恶性细胞中，主要起作用的蛋白激酶是PKCε，在逆转细胞中活力降低的也是PKCε; 使PKCε抑制的则是C/EBPβ 3'UTR RNA。在体外实验中，C/EBPβ 3'UTR RNA能抑制PKCε的活力；在细胞内，C/EBPβ 3'UTR RNA通过与PKCε和细胞角蛋白18三者形成复合物，使PKCε对其靶蛋白的磷酸化活力被抑制，因此导致细胞恶性度降低。
该项研究工作得到国家自然科学基金资助。（生物谷Bioon.com）
生物谷推荐原文出处：
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.
