Altered Expression of Transfer-RNA-Derived Small RNAs in Human With Rheumatic Heart Disease

Abstract

Rheumatic heart disease (RHD) remains a severe public health problem in developing countries. Atrial fibrillation (AF) is a medical complication of RHD. Although the understanding of disease pathogenesis has advanced in recent years, the key questions need to be addressed. Transfer RNA–derived small RNAs (tsRNAs) are a novel type of short non-coding RNAs with potential regulatory functions in various physiological and pathological processes. The present study used tsRNAs sequencing to investigate the relationship between RHD and atrial fibrillation (AF). Three paired cardiac papillary muscles were taken from six rheumatic RHD patients with AF (3 cases) or without AF (3 cases) from January 2016 to January 2017 in Xiangya Hospital, Central South University. A total of 219 precisely matched tsRNAs were identified, and 77 tsRNAs (fold change > 2.0 and P < 0.05) were differently changed. Three tsRNAs (AS-tDR-001269, AS-tDR-001363, AS-tDR-006049) were randomly selected and confirmed by qRT-PCR. The results of qRT-PCR were consistent with tsRNAs sequencing, suggesting the tsRNAs sequencing was reliable. Subsequently, we predicted the target mRNAs of the three tsRNAs. Moreover, we verified the functions of tsRNAs targeting mRNAs in vitro. Finally, bioinformatics analysis indicated that the target genes were abundant in regulation of transcription, DNA binding, intracellular. Most of the genes were predicted to interplay with cytokine-cytokine receptor by KEGG analysis. Our findings uncover the pathological process of AF in RHD through tsRNAs sequencing. This research provides a new perspective for future research on elucidating the mechanism of AF in RHD and offers potential new candidates for the treatment and diagnosis.

Transfer RNA-derived small RNA tRF-Glu-CTC attenuates neointimal formation via inhibition of fibromodulin

“…tsRNAs have been identified as biomarkers or potential therapeutic targets in many cardiovascular diseases, including rheumatic heart disease [ 40 ], cardiac hypertrophy [ 13 ], heart failure [ 16 ], atherosclerosis [ 41 ], and aortic dissection [ 42 ]. There is evidence that tsRNAs regulate the proliferation [ 43 ] and phenotypic switching [ 44 ] of VSMCs.…”

Microarray Analysis Reveals Changes in tRNA-Derived Small RNAs (tsRNAs) Expression in Mice with Septic Cardiomyopathy

“…For example, tRFs are involved in isoprenaline myocardial hypertrophy in Sprague-Dawley rats, perhaps specifically because tRF-5 binds to the 3′ UTR of the hypertrophy regulator TIMP3 mRNA and inhibits its expression, which leads to hypertrophy of cardiac myocytes [ 35 ]. In addition, Yang et al screened 77 tsRNAs that might be involved in rheumatic heart disease with atrial fibrillation by RNA sequencing, providing a reference for us to explore the regulatory role of tsRNA in rheumatic heart disease with atrial fibrillation [ 36 ]. tsRNA has also been studied in fulminant myocarditis [ 37 ], myocardial ischemia [ 38 ], and arteriosclerosis [ 39 ].…”

Small non‐coding RNA signatures in atrial appendages of patients with atrial fibrillation

“…To our knowledge, only two studies have explored the role of tsRNAs in AF. 13 , 14 One study examined the tsRNA expression profiles in three pairs of AF and control heart tissues using high‐throughput sequencing. 13 Another study found that tsRNA‐5008a was highly expressed in an AF mouse model and promoted myocardial fibrosis by targeting SLC7A11.…”

“… 13 , 14 One study examined the tsRNA expression profiles in three pairs of AF and control heart tissues using high‐throughput sequencing. 13 Another study found that tsRNA‐5008a was highly expressed in an AF mouse model and promoted myocardial fibrosis by targeting SLC7A11. 14 Other sncRNAs, such as snoRNAs or piRNAs, have not been studied in AF.…”