ADP-ribosylation (ADPRylation) is a posttranslational modification of proteins discovered nearly six decades ago, but many important questions remain regarding its molecular functions and biological roles, as well as the activity of the ADP-ribose (ADPR) transferase enzymes (PARP family members) that catalyze it. Growing evidence indicates that PARP-mediated ADPRylation events are key regulators of the protein biosynthetic pathway, leading from rDNA transcription and ribosome biogenesis to mRNA synthesis, processing, and translation. In this review we describe the role of PARP proteins and ADPRylation in all facets of this pathway. PARP-1 and its enzymatic activity are key regulators of rDNA transcription, which is a critical step in ribosome biogenesis. An emerging role of PARPs in alternative splicing of mRNAs, as well as direct ADPRylation of mRNAs, highlight the role of PARP members in RNA processing. Furthermore, PARP activity, stimulated by cellular stresses, such as viral infections and ER stress, leads to the regulation of mRNA stability and protein synthesis through posttranscriptional mechanisms. Dysregulation of PARP activity in these processes can promote disease states. Collectively, these results highlight the importance of PARP family members and ADPRylation in gene regulation, mRNA processing, and protein abundance. Future studies in these areas will yield new insights into the fundamental mechanisms and a broader utility for PARP-targeted therapeutic agents.

中文翻译：

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RNA生物学中的PARP和ADP-核糖基化：从RNA表达和加工到蛋白质翻译和蛋白稳定。

ADP-核糖基化（ADPRylation）是将近六十年前发现的蛋白质的翻译后修饰，但关于其分子功能和生物学作用以及ADP-核糖（ADPR）转移酶的活性（PARP家族成员）仍存在许多重要问题）来催化它。越来越多的证据表明，从rDNA转录和核糖体生物发生到mRNA合成，加工和翻译，PARP介导的ADPR酰化事件是蛋白质生物合成途径的关键调节因子。在这篇综述中，我们描述了PARP蛋白和ADPRylation在该途径所有方面的作用。PARP-1及其酶活性是rDNA转录的关键调节因子，这是核糖体生物发生的关键步骤。PARP在mRNA选择性剪接中的新兴作用，以及mRNA的直接ADPRylation，突出了PARP成员在RNA加工中的作用。此外，受细胞应激（例如病毒感染和内质网应激）刺激的PARP活性通过转录后机制导致mRNA稳定性和蛋白质合成的调控。在这些过程中，PARP活性的失调可促进疾病状态。总的来说，这些结果突出了PARP家族成员和ADPRylation在基因调控，mRNA加工和蛋白质丰度中的重要性。在这些领域的未来研究将获得针对PARP靶向治疗剂的基本机制和更广泛用途的新见解。通过转录后机制导致mRNA稳定性和蛋白质合成的调控。在这些过程中，PARP活性的失调可促进疾病状态。总的来说，这些结果突出了PARP家族成员和ADPRylation在基因调控，mRNA加工和蛋白质丰度中的重要性。在这些领域的未来研究将获得针对PARP靶向治疗剂的基本机制和更广泛用途的新见解。通过转录后机制导致mRNA稳定性和蛋白质合成的调控。在这些过程中，PARP活性的失调可促进疾病状态。总的来说，这些结果突出了PARP家族成员和ADPRylation在基因调控，mRNA加工和蛋白质丰度中的重要性。在这些领域的未来研究将获得针对PARP靶向治疗剂的基本机制和更广泛用途的新见解。