Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM), Universiteitssingel 50, 6229 Maastricht University, Maastricht, The Netherlands.
The Division of Cardiology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Cardiovasc Res. 2022 Mar 16;118(4):1004-1019. doi: 10.1093/cvr/cvab117.
The human transcriptome comprises a complex network of coding and non-coding RNAs implicated in a myriad of biological functions. Non-coding RNAs exhibit highly organized spatial and temporal expression patterns and are emerging as critical regulators of differentiation, homeostasis, and pathological states, including in the cardiovascular system. This review defines the current knowledge gaps, unmet methodological needs, and describes the challenges in dissecting and understanding the role and regulation of the non-coding transcriptome in cardiovascular disease. These challenges include poor annotation of the non-coding genome, determination of the cellular distribution of transcripts, assessment of the role of RNA processing and identification of cell-type specific changes in cardiovascular physiology and disease. We highlight similarities and differences in the hurdles associated with the analysis of the non-coding and protein-coding transcriptomes. In addition, we discuss how the lack of consensus and absence of standardized methods affect reproducibility of data. These shortcomings should be defeated in order to make significant scientific progress and foster the development of clinically applicable non-coding RNA-based therapeutic strategies to lessen the burden of cardiovascular disease.
人类转录组由编码和非编码 RNA 组成的复杂网络组成，这些 RNA 参与了多种生物学功能。非编码 RNA 表现出高度组织化的时空表达模式，并且作为分化、内稳态和病理状态（包括心血管系统）的关键调节剂而出现。本综述定义了当前的知识空白、未满足的方法学需求，并描述了在剖析和理解非编码转录组在心血管疾病中的作用和调控方面所面临的挑战。这些挑战包括非编码基因组注释不良、确定转录本的细胞分布、评估 RNA 加工的作用以及鉴定心血管生理学和疾病中细胞类型特异性的变化。我们强调了分析非编码和编码转录组所涉及的相似和不同的障碍。此外，我们还讨论了缺乏共识和缺乏标准化方法如何影响数据的可重复性。为了取得重大的科学进展并促进基于非编码 RNA 的治疗策略的临床应用，以减轻心血管疾病的负担，这些缺点应该得到克服。
