Department of Ecological and Biological Sciences, University of Tuscia, Viterbo, Italy.
Department of Anatomical, Histological, Forensic & Orthopedic Sciences, Section of Histology & Medical Embryology, Sapienza University of Rome, Laboratory affiliated with Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Rome 00161, Italy.
Biochim Biophys Acta Mol Basis Dis. 2021 Apr 1;1867(4):166046. doi: 10.1016/j.bbadis.2020.166046. Epub 2020 Dec 28.
Tight control of mRNA expression is required for cell differentiation; imbalanced regulation may lead to developmental disorders and cancer. The activity of the translational machinery (including ribosomes and translation factors) regulates the rate (slow or fast) of translation of encoded proteins, and the quality of these proteins highly depends on which mRNAs are available for translation. Specific RNA-binding and ribosomal proteins seem to play a key role in controlling gene expression to determine the differentiation fate of the cell. This demonstrates the important role of RNA-binding proteins, specific ribosome-binding proteins and microRNAs as key molecules in controlling the specific proteins required for the differentiation or dedifferentiation of cells. This delicate balance between specific proteins (in terms of quality and availability) and post-translational modifications occurring in the cytoplasm is crucial for cell differentiation, dedifferentiation and oncogenic potential. In this review, we report how defects in the regulation of mRNA translation can be dependent on specific proteins and can induce an imbalance between differentiation and dedifferentiation in cell fate determination.
需要严格控制 mRNA 表达以实现细胞分化;失衡的调控可能导致发育障碍和癌症。翻译机制(包括核糖体和翻译因子)的活性调节编码蛋白的翻译速度(缓慢或快速),这些蛋白的质量在很大程度上取决于可用于翻译的 mRNA。特定的 RNA 结合蛋白和核糖体蛋白似乎在控制基因表达以决定细胞的分化命运方面发挥着关键作用。这表明 RNA 结合蛋白、特定的核糖体结合蛋白和 microRNA 作为关键分子在控制细胞分化或去分化所需的特定蛋白方面具有重要作用。这种特定蛋白质(在质量和可用性方面)和细胞质中发生的翻译后修饰之间的微妙平衡对于细胞分化、去分化和致癌潜能至关重要。在这篇综述中,我们报告了 mRNA 翻译调控的缺陷如何依赖于特定的蛋白质,并可能导致细胞命运决定中分化和去分化之间的失衡。