Zhang Li, Tang Mi, Diao Haoyang, Xiong Liling, Yang Xiao, Xing Shasha
Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, 1617 Riyue Street, Qingyang District, Chengdu 611731, China.
Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China.
Cardiovasc Res. 2023 Oct 16;119(12):2165-2178. doi: 10.1093/cvr/cvad112.
Long non-coding RNAs (lncRNAs), which are RNA transcripts exceeding 200 nucleotides were believed to lack any protein-coding capacity. But advancements in -omics technology have revealed that some lncRNAs have small open reading frames (sORFs) that can be translated by ribosomes to encode peptides, some of which have important biological functions. These encoded peptides subserve important biological functions by interacting with their targets to modulate transcriptional or signalling axes, thereby enhancing or suppressing cardiovascular disease (CVD) occurrence and progression. In this review, we summarize what is known about the research strategy of lncRNA-encoded peptides, mainly comprising predictive websites/tools and experimental methods that have been widely used for prediction, identification, and validation. More importantly, we have compiled a list of lncRNA- encoded peptides, with a focus on those that play significant roles in cardiovascular physiology and pathology, including ENSRNOT (RNO)-sORF6/RNO-sORF7/RNO-sORF8, dwarf open reading frame (DOWRF), myoregulin (NLN), etc. Additionally, we have outlined the functions and mechanisms of these peptides in cardiovascular physiology and pathology, such as cardiomyocyte hypertrophy, myocardial contraction, myocardial infarction, and vascular remodelling. Finally, an overview of the existing challenges and potential future developments in the realm of lncRNA-encoded peptides was provided, with consideration given to prospective avenues for further research. Given that many lncRNA-encoded peptides have not been functionally annotated yet, their application in CVD diagnosis and treatment still requires further research.
长链非编码RNA（lncRNAs）是长度超过200个核苷酸的RNA转录本，曾被认为缺乏任何蛋白质编码能力。但是组学技术的进步表明，一些lncRNAs具有小开放阅读框（sORFs），这些开放阅读框可以被核糖体翻译以编码肽段，其中一些肽段具有重要的生物学功能。这些编码的肽段通过与其靶标相互作用来调节转录或信号轴，从而增强或抑制心血管疾病（CVD）的发生和发展，进而发挥重要的生物学功能。在本综述中，我们总结了关于lncRNA编码肽段的研究策略，主要包括已广泛用于预测、鉴定和验证的预测网站/工具和实验方法。更重要的是，我们编制了一份lncRNA编码肽段的清单，重点关注那些在心血管生理和病理中起重要作用的肽段，包括ENSRNOT（RNO）-sORF6/RNO-sORF7/RNO-sORF8、矮小开放阅读框（DOWRF）、肌调节蛋白（NLN）等。此外，我们概述了这些肽段在心血管生理和病理中的功能和机制，如心肌细胞肥大、心肌收缩、心肌梗死和血管重塑。最后，对lncRNA编码肽段领域现有的挑战和潜在的未来发展进行了概述，并考虑了进一步研究的前瞻性途径。鉴于许多lncRNA编码肽段尚未进行功能注释，它们在CVD诊断和治疗中的应用仍需要进一步研究。
