Medical Research Council Toxicology Unit, Leicester, UK.
Curr Protein Pept Sci. 2012 Jun;13(4):294-304. doi: 10.2174/138920312801619475.
A growing body of work demonstrates the importance of post-transcriptional control, in particular translation initiation, in the overall regulation of gene expression. Here we focus on the contribution of regulatory elements within the 5' and 3' untranslated regions of mRNA to gene expression in eukaryotic cells including terminal oligopyrimidine tracts, internal ribosome entry segments, upstream open reading frames and cytoplasmic polyadenylation elements. These mRNA regulatory elements may adopt complex secondary structures and/or contain sequence motifs that allow their interaction with a variety of regulatory proteins, RNAs and RNA binding proteins, particularly hnRNPs. The resulting interactions are context-sensitive, and provide cells with a sensitive and fast response to cellular signals such as hormone exposure or cytotoxic stress. Importantly, an increasing number of diseases have been identified, particularly cancers and those associated with neurodegeneration, which originate either from mutation of these regulatory motifs, or from deregulation of their cognate binding partners.
越来越多的研究表明，转录后调控，特别是翻译起始，在基因表达的整体调控中具有重要作用。在这里，我们主要关注 mRNA 5' 和 3' 非翻译区中的调节元件对真核细胞中基因表达的贡献，包括末端寡嘧啶序列、内部核糖体进入序列、上游开放阅读框和细胞质多聚腺苷酸化元件。这些 mRNA 调节元件可能形成复杂的二级结构，或包含序列基序，允许它们与各种调节蛋白、RNA 和 RNA 结合蛋白相互作用，特别是 hnRNPs。由此产生的相互作用具有上下文敏感性，使细胞能够对细胞信号（如激素暴露或细胞毒性应激）做出敏感和快速的反应。重要的是，越来越多的疾病已被确定，特别是癌症和与神经退行性变相关的疾病，这些疾病要么源于这些调节基序的突变，要么源于其同源结合伙伴的失调。
