The significance of small noncoding RNAs in the pathogenesis of cardiovascular diseases

Abstract

With the advancement of high-throughput sequencing and bioinformatics, an increasing number of overlooked small noncoding RNAs (sncRNAs) have emerged. These sncRNAs predominantly comprise transfer RNA-derived fragments (tsRNAs), PIWI-interacting RNAs (piRNAs), Ro-associated non-coding RNAs (RNYs or Y-RNAs), small nucleolar RNAs (snoRNAs), and small nuclear RNAs (snRNAs). Each of these RNA types possesses distinct biological properties and plays specific roles in both physiological and pathological processes. The differential expression of sncRNAs substantially affects the occurrence and progression of various systemic diseases. However, their roles in the cardiovascular system remain unclear. Therefore, understanding the functionality and mechanisms of sncRNAs in the cardiovascular system holds promise for identifying novel targets and strategies for the diagnosis, prevention, and treatment of cardiovascular diseases. This review examines the biological characteristics of sncRNAs and their potential roles in cardiovascular diseases.

Keywords: Biological function; Biomarkers; Cardiovascular diseases; Gene regulation; SncRNA.

Figure 1

The classification of tsRNAs. tsRNAs include tiRNA and tRF. Under stress, angiogenin cleavage of the tRNA anticodon loop generates tiRNAs that are further categorized as 5′ tiRNA and 3′ tiRNA. Five types of tRF are generated: tRF-1, precursor tRNA produced by RNAse ZL/ELAC2 mediation in the cell nucleus; tRF-3a and tRF-3b originate from T-loop of mature tRNA; tRF-5a, b, and c subtypes are derived from D-loop of tRNA; tRF-2 and i-tRF are generated from anticodon loop of mature tRNA. The orange in the figure represents the pathway generated after D-loop cleavage, the yellow represents the pathway generated after anticodon loop cleavage, and the green represents the pathway generated after T-loop cleavage. ANG, angiogenin; tRNA, transfer RNA; tiRNA, tRNA-derived stress-induced RNAs, tRF, tRNA-derived fragments; tsRNAs, transfer RNA-derived fragments.

Figure 2

piRNA biogenesis pathways in drosophila. The biogenesis pathways of piRNA involve primary and secondary pathways. The primary pathway entails the transcription of precursor piRNA from piRNA clusters, which is then loaded onto PIWI proteins to form a complex. The secondary pathway, also known as the ping-pong cycle, is initiated by the Aub-piRNA complex, leading to the amplification of the ping-pong mechanism. Subsequently, the mutual cleavage of complementary transcripts from transposons and pre-piRNA results in the generation of a large quantity of piRNA. piRNA, PIWI-interacting RNAs.

Figure 3

The categorization of PIWI family proteins. piRNA primarily engages in physiological functions by binding with PIWI proteins within reproductive cells, encompassing family proteins in humans, mice, and drosophila. The primary functions of piRNAs include cleaving transposon transcripts to function in post-transcriptional gene silencing, participate in gene regulation during gonadal development, and maintain genomic integrity by suppressing transposable elements (TEs). piRNA, PIWI-interacting RNAs.