Since the introduction of the central dogma of molecular biology in 1958, various RNA species have been discovered. Messenger RNAs transmit genetic instructions from DNA to make proteins, a process facilitated by housekeeping non-coding RNAs (ncRNAs) such as small nuclear RNAs (snRNAs), ribosomal RNAs (rRNAs), and transfer RNAs (tRNAs). Over the past four decades, a wide array of regulatory ncRNAs have emerged as crucial players in gene regulation. In celebration of Cell’s 50th anniversary, this Review explores our current understanding of the most extensively studied regulatory ncRNAs—small RNAs and long non-coding RNAs (lncRNAs)—which have profoundly shaped the field of RNA biology and beyond. While small RNA pathways have been well documented with clearly defined mechanisms, lncRNAs exhibit a greater diversity of mechanisms, many of which remain unknown. This Review covers pivotal events in their discovery, biogenesis pathways, evolutionary traits, action mechanisms, functions, and crosstalks among ncRNAs. We also highlight their roles in pathophysiological contexts and propose future research directions to decipher the unknowns of lncRNAs by leveraging lessons from small RNAs.

中文翻译：

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小而长的非编码 RNA：过去、现在和未来


自 1958 年引入分子生物学的中心法则以来，已经发现了各种 RNA 种类。信使 RNA 传递来自 DNA 的遗传指令以制造蛋白质，这一过程由小核 RNA （snRNA）、核糖体 RNA （rRNA） 和转移 RNA （tRNA） 等非编码 RNA （ncRNA） 的管家化促进。在过去的四十年中，各种调节性 ncRNA 已成为基因调控的关键参与者。为庆祝 Cell 成立 50 周年，本综述探讨了我们目前对研究最广泛的调节性 ncRNA（小 RNA 和长链非编码 RNA （lncRNA））的理解，它们深刻地塑造了 RNA 生物学及其他领域。虽然小 RNA 通路已经有明确定义的机制，但 lncRNA 表现出更多样化的机制，其中许多机制仍然未知。本综述涵盖了其发现、生物发生途径、进化特征、作用机制、功能和 ncRNA 之间的串扰中的关键事件。我们还强调了它们在病理生理学背景下的作用，并提出了未来的研究方向，以利用小 RNA 的经验来破译 lncRNAs 的未知数。