Novel and Annotated Long Noncoding RNAs Associated with Ischemia in the Human Heart

Abstract

Background: Long noncoding RNAs (lncRNAs) have been implicated in the pathogenesis of cardiovascular diseases. We aimed to identify novel lncRNAs associated with the early response to ischemia in the heart. Methods and Results: RNA sequencing data gathered from 81 paired left ventricle samples from patients undergoing cardiopulmonary bypass was collected before and after a period of ischemia. Novel lncRNAs were validated with Oxford Nanopore Technologies long-read sequencing. Gene modules associated with an early ischemic response were identified and the subcellular location of selected lncRNAs was determined with RNAscope. A total of 2446 mRNAs, 270 annotated lncRNAs and one novel lncRNA differed in response to ischemia (adjusted p < 0.001, absolute fold change >1.2). The novel lncRNA belonged to a gene module of highly correlated genes that also included 39 annotated lncRNAs. This module associated with ischemia (Pearson correlation coefficient = −0.69, p = 1 × 10−23) and activation of cell death pathways (p < 6 × 10−9). A further nine novel cardiac lncRNAs were identified, of which, one overlapped five cis-eQTL eSNPs for the gene RWD Domain-Containing Sumoylation Enhancer (RWDD3) and was itself correlated with RWDD3 expression (Pearson correlation coefficient −0.2, p = 0.002). Conclusion: We have identified 10 novel lncRNAs, one of which was associated with myocardial ischemia and may have potential as a novel therapeutic target or early marker for myocardial dysfunction.

Transcriptional changes during isoproterenol-induced cardiac fibrosis in mice

“…For expression estimation and transcript-level expression profiling, StringTie was then utilized in conjunction with GENCODE v25 ( https://www.gencodegenes.org/mouse/ ) as the reference annotation file. Subsequently, a set of inclusion criteria was applied to the transcripts obtained from the output GTF file ( Ounzain et al, 2015 ; Azlan et al, 2019 ; Ward et al, 2021 ). The criteria were as follows: (i) the transcripts should be multi-exonic; (ii) they should correspond to gffcompare v0.11.2 ( Pertea and Pertea, 2020 ) class codes ‘u' (intergenic), ‘i' (intronic), ‘x' (antisense), or ‘y' (containing a reference gene within its intron) based on the reference annotation GENCODE v25 ( Ward et al, 2021 ); (iii) the transcript length should exceed 200 nucleotides; (iv) the transcripts should align to the autosomes or the X chromosome; (v) they should lack coding potential and possess an open reading frame (ORF) shorter than 300, as assessed by the Coding Potential Assessment Tool (CPAT v3.0) ( Clark et al, 2015 ; Chen et al, 2016 ) using default settings,; (vi) transcripts identified as coding regions by TransDecoder v5.5 ( https://github.com/TransDecoder/TransDecoder ) and those with homology to the UniProt dataset determined by BLASTP were discarded; (vii) transcripts with significant hits for known protein domains, identified using HMMER against the Pfam database ( Finn et al, 2014 ), were also discarded; and (viii) transcripts with a read count less than 5 across all samples were excluded.…”

Identifying Candidate Circulating RNA Markers for Coronary Artery Disease by Deep RNA-Sequencing in Human Plasma

“…The bioinformatics pipeline was designed to detect mRNAs, lncRNAs and circRNAs and generate data on putative novel lncRNA and circRNA transcripts (summarised in Supplementary Figure S2 ) [ 29 ]. The pipeline is freely available to download at , accessed on 20 August 2018.…”

Impact of RSUME Actions on Biomolecular Modifications in Physio-Pathological Processes

“…Besides its role in tumor progression, recent studies reveal that RSUME is connected with cardiac tissue response to ischemia and stroke ( 18 , 19 ) ( Figure 2 ). Enhanced SUMOylation has been proposed to protect from stroke and ischemia of the brain ( 20 , 21 ).…”

“…Ward et al. carried out a detailed study in which the comparison of ventricular tissue after and before ischemia in humans shows that several long non-coding RNAs (lncRNAs) are differentially expressed and related to fast response to ventricular ischemia ( 18 ). From the novel lncRNA group, a particular lncRNA targets five regulatory loci (expression quantitative trait loci, eQTL) for RSUME, and consequently, this lncRNA’s expression correlates with RSUME expression in this study group ( 18 ).…”