Dreyfuss Gideon
Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
RNA. 2025 Feb 19;31(3):277-283. doi: 10.1261/rna.080353.124.
All RNAs exist in complexes (RNPs) with RNA-binding proteins (RBPs). Studies in my lab since the 1980s have identified, sequenced and characterized the major pre-mRNA- and mRNA-RBPs (hnRNPs/mRNPs), revealing RNA-binding domains and common features of numerous RBPs and their central roles in posttranscriptional gene regulation. The first links between RBPs and RNPs to diseases emerged serendipitously for fragile X syndrome, as its gene () encoded RBP (FMRP), and spinal muscular atrophy (SMA), caused by deficits in survival motor neurons (SMN). Discoveries of the SMN complex and its unanticipated function in RNP assembly, essential for spliceosomal snRNP biogenesis, advanced understanding of RNA biology and pathogenesis. I reflect on how these and other contributions (e.g., nucleocytoplasmic shuttling, telescripting) originated from curiosity-driven exploration and highly collaborative lab culture. The vast RNA and RBP assortments are beneficial, but increase complexity and chances of disorders, making the RNP sphere a rich source for future discoveries.
所有RNA都与RNA结合蛋白（RBP）形成复合物（RNP）存在。自20世纪80年代以来，我实验室的研究已鉴定、测序并表征了主要的前体mRNA和mRNA-RBP（hnRNP/mRNP），揭示了众多RBP的RNA结合结构域和共同特征，以及它们在转录后基因调控中的核心作用。RBP和RNP与疾病之间的最初联系是在脆性X综合征中偶然发现的，因为其基因（）编码RBP（FMRP），以及脊髓性肌萎缩症（SMA），它是由存活运动神经元（SMN）缺陷引起的。SMN复合物及其在RNP组装中意外功能的发现，对剪接体snRNP生物合成至关重要，推动了对RNA生物学和发病机制的深入理解。我反思了这些以及其他贡献（例如，核质穿梭、远程转录）是如何源于好奇心驱动的探索和高度协作的实验室文化。庞大的RNA和RBP种类是有益的，但增加了复杂性和出现紊乱的可能性，使RNP领域成为未来发现的丰富来源。
