Non-coding RNAs (ncRNAs) constitute the majority of the human transcriptome and play diverse structural, catalytic, and regulatory roles. The ability of ncRNAs to be translated into functional peptides and microproteins expands our understanding of their regulatory potential beyond their established non-coding functions. Our comprehensive search identified 86 translating “non-coding” RNAs. While translating ncRNAs have traditionally been categorized as “peptide-encoding”, in this study, we introduce a novel classification based on amino acid length, distinguishing their products as ncRNA encoded peptides (ncRNA-PEPs), which are less than 60 amino acids, or ncRNA encoded microproteins (ncRNA-MPs) ranging from 61 to 200 amino acids. These peptides and microproteins act as co-regulators in cell signaling, transcriptional regulation, and protein complex assembly, playing a role in both health and disease. We outline the molecular pathways by which ncRNA-PEPs and ncRNA-MPs could govern cell cycle progression, highlighting their influence on cell cycle transitions, oncogenic and tumor suppressor pathways, metabolic homeostasis, autophagy, and on key cell cycle regulators like PCNA, Rad18, and CDK–cyclin complexes. Furthermore, we highlight recent advancements in their detection and characterization, exploring their evolutionary origins, species-specific conservation, and potential therapeutic applications. Our findings underscore the emerging significance of ncRNA-PEPs and ncRNA-MPs as integral regulators of cellular processes, highlighting their functional versatility and opening promising avenues for further research and potential therapeutic applications.
非编码RNA(ncRNA)构成了人类转录组的主要部分,并在结构、催化和调控方面发挥多样化作用。ncRNA能够被翻译成功能性肽段和微蛋白,这一特性拓展了我们对它们调控潜力的理解,超越了其既定的非编码功能。通过全面检索,我们鉴定出86个具有翻译潜力的“非编码”RNA。传统上,具有翻译能力的ncRNA被归类为“肽编码”RNA,而在本研究中,我们基于氨基酸长度提出了一种新的分类方法,将其产物区分为ncRNA编码肽(ncRNA-PEPs,长度小于60个氨基酸)和ncRNA编码微蛋白(ncRNA-MPs,长度在61至200个氨基酸之间)。这些肽段和微蛋白在细胞信号传导、转录调控和蛋白质复合物组装中作为共调控因子发挥作用,参与健康与疾病过程。我们概述了ncRNA-PEPs和ncRNA-MPs调控细胞周期进程的分子通路,重点阐明了它们对细胞周期转换、致癌与抑癌通路、代谢稳态、自噬以及对PCNA、Rad18和CDK–cyclin复合物等关键细胞周期调控因子的影响。此外,我们强调了其检测与表征技术的最新进展,探讨了它们的进化起源、物种特异性保守性以及潜在的治疗应用前景。我们的研究结果凸显了ncRNA-PEPs和ncRNA-MPs作为细胞过程核心调控因子的新兴重要性,揭示了其功能多样性,并为未来研究和潜在治疗应用开辟了前景广阔的途径。
Beyond the Transcript: Translating Non-Coding RNAs and Their Impact on Cellular Regulation