School of Pharmacy, Shenzhen University Medical School, Shenzhen, 518055, China.
Institute of Biomedicine, College of Life Science and Technology, Guangdong Province Key Laboratory of Bioengineering Medicine, Key Laboratory of Innovative Technology Research On Natural Products and Cosmetics Raw Materials, Jinan University, Guangzhou, 510632, China.
Cell Mol Life Sci. 2023 May 17;80(6):153. doi: 10.1007/s00018-023-04808-6.
Accumulating evidence has consolidated the interaction between viral infection and host alternative splicing. Serine-arginine (SR) proteins are a class of highly conserved splicing factors critical for the spliceosome maturation, alternative splicing and RNA metabolism. Serine-arginine protein kinases (SRPKs) are important kinases that specifically phosphorylate SR proteins to regulate their distribution and activities in the central pre-mRNA splicing and other cellular processes. In addition to the predominant SR proteins, other cytoplasmic proteins containing a serine-arginine repeat domain, including viral proteins, have been identified as substrates of SRPKs. Viral infection triggers a myriad of cellular events in the host and it is therefore not surprising that viruses explore SRPKs-mediated phosphorylation as an important regulatory node in virus-host interactions. In this review, we briefly summarize the regulation and biological function of SRPKs, highlighting their involvement in the infection process of several viruses, such as viral replication, transcription and capsid assembly. In addition, we review the structure-function relationships of currently available inhibitors of SRPKs and discuss their putative use as antivirals against well-characterized viruses or newly emerging viruses. We also highlight the viral proteins and cellular substrates targeted by SRPKs as potential antiviral therapeutic candidates.
越来越多的证据证实了病毒感染与宿主可变剪接之间的相互作用。丝氨酸/精氨酸（SR）蛋白是一类高度保守的剪接因子，对于剪接体成熟、可变剪接和 RNA 代谢至关重要。丝氨酸/精氨酸蛋白激酶（SRPKs）是重要的激酶，可特异性磷酸化 SR 蛋白，以调节其在中央前体 mRNA 剪接和其他细胞过程中的分布和活性。除了主要的 SR 蛋白外，其他含有丝氨酸-精氨酸重复结构域的细胞质蛋白，包括病毒蛋白，已被鉴定为 SRPKs 的底物。病毒感染会引发宿主细胞内的一系列反应，因此病毒利用 SRPKs 介导的磷酸化作为病毒-宿主相互作用中的一个重要调控节点也就不足为奇了。在这篇综述中，我们简要总结了 SRPKs 的调控和生物学功能，重点介绍了它们在几种病毒感染过程中的作用，如病毒复制、转录和衣壳组装。此外，我们还回顾了目前可用的 SRPKs 抑制剂的结构-功能关系，并讨论了它们作为针对已知病毒或新出现病毒的抗病毒药物的潜在用途。我们还强调了 SRPKs 靶向的病毒蛋白和细胞底物作为潜在抗病毒治疗候选物的重要性。
