Abstract：
RNA-binding proteins (RBPs) are evolutionarily conserved across most forms of life, with an estimated 1500 RBPs in humans. Traditionally associated with post-transcriptional gene regulation, RBPs contribute to nearly every known aspect of RNA biology, including RNA splicing, transport, and decay. In recent years, an increasing subset of RBPs have been recognized for their DNA binding properties and involvement in DNA transactions. We refer to these RBPs with well-characterized DNA binding activity as RNA/DNA binding proteins (RDBPs), many of which are linked to neurological diseases. RDBPs are associated with both nuclear and mitochondrial DNA repair. Furthermore, the presence of intrinsically disordered domains in RDBPs appears to be critical for regulating their diverse interactions and plays a key role in controlling protein aggregation, which is implicated in neurodegeneration. In this review, we discuss the emerging roles of common RDBPs from the heterogeneous nuclear ribonucleoprotein (hnRNP) family, such as TAR DNA binding protein-43 (TDP43) and fused in sarcoma (FUS) in controlling DNA damage response (DDR). We also explore the implications of RDBP pathology in aging and neurodegenerative diseases and provide a prospective on the therapeutic potential of targeting RDBP pathology mediated DDR defects for motor neuron diseases and aging.
摘要：
RNA结合蛋白（RBP）在大多数生命形式中都是进化保守的，人类估计有1500个RBPs。传统上与转录后基因调控相关，RBP几乎对RNA生物学的每个已知方面都有贡献，包括RNA剪接，运输,和衰变。近年来,越来越多的RBP子集因其DNA结合特性和参与DNA交易而得到认可。我们将这些具有良好表征的DNA结合活性的RBP称为RNA/DNA结合蛋白（RDBPs），其中许多与神经系统疾病有关。RDBPs与核和线粒体DNA修复有关。此外，RDBPs中固有无序结构域的存在似乎对于调节它们的不同相互作用至关重要，并且在控制蛋白质聚集中起着关键作用。这与神经变性有关。在这次审查中,我们讨论了来自异质核核糖核蛋白（hnRNP）家族的常见RDBPs的新兴作用，如TARDNA结合蛋白-43（TDP43）和融合在肉瘤（FUS）中控制DNA损伤反应（DDR）。我们还探讨了RDBP病理在衰老和神经退行性疾病中的意义，并提供了针对RDBP病理介导的DDR缺陷对运动神经元疾病和衰老的治疗潜力的前瞻性。
