CHKB divergent transcript (CHKB-DT)

CHKB divergent transcript (CHKB-DT) is a long noncoding RNA (lncRNA) with recently described key roles in cardiac energy metabolism and disease, particularly dilated cardiomyopathy. It is located near the CHKB (choline kinase beta) gene locus, distinct from the CHKB protein-coding sequence, and does not code for a protein. CHKB-DT is highly enriched in heart tissue and significantly downregulated in human and mouse models of dilated cardiomyopathy. Experimental studies show that lowering CHKB-DT levels in cardiomyocytes leads to impaired mitochondrial function, reduced ATP production, and increased susceptibility to cardiac dysfunction. Mechanistically, CHKB-DT physically interacts with ALDH2 mRNA and the RNA-binding protein FUS, enhancing the stability of ALDH2 transcript and mitigating the accumulation of toxic oxidative metabolites (such as 4-hydroxy-2-nonenal). Restoration of ALDH2 in models with reduced CHKB-DT expression can rescue mitochondrial and cardiac function. CHKB-DT knockdown impairs energy metabolism and mitochondrial function, aggravates cardiac dilation and dysfunction, and destabilizes ALDH2 mRNA in animal models. Conversely, overexpression of CHKB-DT or restoration of its molecular targets alleviates cardiac dysfunction in these models. Thus, CHKB-DT is emerging as a critical RNA regulator of cardiac metabolism and a promising therapeutic and biomarker candidate in cardiovascular disease, though no drugs currently target it directly. It does not code for a protein and is not a receptor, enzyme, transporter, or transcription factor, but rather acts through post-transcriptional and RNA-interaction pathways. Clinical translation is in early stages; it is best described as a noncoding RNA with strong emerging evidence for its role in cardiac pathophysiology.

Other names

lncRNA-Hypoxia/reoxygenation-associated transcriptTCONS_00029632HRATCHKB-AS1CHKB antisense RNA 1 (head to head)CTA-384D8.20

Not applicable/No approved drugs currently target CHKB-DT. Biologically, overexpression or restoration of CHKB-DT rescues ALDH2 mRNA stability, improves mitochondrial function, and enhances cardiac performance by interacting with ALDH2 mRNA and the RNA-binding protein FUS.