Laboratory of Molecular Biology and Immunology, National Institute on Aging - Intramural Research Program, NIH, Baltimore, MD 21224, USA.
Nucleic Acids Res. 2011 Oct;39(19):8513-30. doi: 10.1093/nar/gkr488. Epub 2011 Jul 6.
RNA-binding proteins (RBPs) regulate gene expression at many post-transcriptional levels, including mRNA stability and translation. The RBP nucleolin, with four RNA-recognition motifs, has been implicated in cell proliferation, carcinogenesis and viral infection. However, the subset of nucleolin target mRNAs and the influence of nucleolin on their expression had not been studied at a transcriptome-wide level. Here, we globally identified nucleolin target transcripts, many of which encoded cell growth- and cancer-related proteins, and used them to find a signature motif on nucleolin target mRNAs. Surprisingly, this motif was very rich in G residues and was not only found in the 3'-untranslated region (UTR), but also in the coding region (CR) and 5'-UTR. Nucleolin enhanced the translation of mRNAs bearing the G-rich motif, since silencing nucleolin did not change target mRNA stability, but decreased the size of polysomes forming on target transcripts and lowered the abundance of the encoded proteins. In summary, nucleolin binds G-rich sequences in the CR and UTRs of target mRNAs, many of which encode cancer proteins, and enhances their translation.
RNA 结合蛋白 (RBPs) 在许多转录后水平上调节基因表达，包括 mRNA 稳定性和翻译。具有四个 RNA 识别基序的 RBP 核仁素与细胞增殖、癌变和病毒感染有关。然而，核仁素的靶 mRNA 亚基及其对其表达的影响尚未在全转录组水平上进行研究。在这里，我们全局鉴定了核仁素靶转录本，其中许多编码与细胞生长和癌症相关的蛋白质，并使用它们在核仁素靶 mRNA 上找到一个特征基序。令人惊讶的是，这个基序富含 G 残基，不仅存在于 3'-非翻译区 (UTR)，也存在于编码区 (CR) 和 5'-UTR。核仁素增强了带有富含 G 基序的 mRNA 的翻译，因为沉默核仁素不会改变靶 mRNA 的稳定性，但会减少在靶转录本上形成的多核糖体的大小，并降低编码蛋白的丰度。总之，核仁素结合靶 mRNA 的 CR 和 UTR 中的富含 G 序列，其中许多编码癌症蛋白，并增强其翻译。
