LncRNA DCRT protects against dilated cardiomyopathy via binding to PTBP1 (Iso-seq)

Dilated cardiomyopathy (DCM) is characterized by left ventricular dilation and continuous systolic dysfunction. Mitochondrial impairment is critical in DCM, but the mechanism remains to be elucidated. Here we explored the cardio-protective role of a heart-enriched long non-coding RNA (lncRNA), named dilated cardiomyopathy repressive transcript (DCRT), via maintaining mitochondrial function. We found the lncRNA DCRT was highly enriched in normal heart tissue and its expression was significantly down-regulated in myocardium of DCM patients. DCRT knockout in mice spontaneously developed cardiac dysfunction with cardiac enlargement and mitochondrial impairment. DCRT transgenic or overexpressed mice attenuated cardiac dysfunction induced by transverse aortic constriction (TAC) treatment. In order to study lncDCRT knockout effect on alternative splicing in AC16 cell lines. We constructed DCRT-knockout (DCRT-KO) cell lines using human cardiomyocyte AC16 via CRISPR-Cas9 strategy. Single-molecule real-time (SMRT) long-read isoform sequencing (Iso-Seq) was performed to detect all the alternative splicing events in DCRT-KO and WT cells >>>Submitter states that they will upload the raw data directly to SRA<<<