tRNA-derived small RNA 3040b (tsRNA-3040b)

tsRNA-3040b is a tRNA-derived small RNA (tsRNA) generated from the cleavage of tRNA-Asp-GTC, which plays a pivotal role in the pathogenesis of pulmonary hypertension (PH). It is significantly upregulated in response to hypoxia, where it functions by promoting the formation of R-loops in the genomic DNA of the Trim35 gene, leading to the inhibition of its transcription [1, 3]. The resulting deficiency in Trim35 protein prevents the ubiquitination and degradation of Wnt3a, thereby activating Wnt signaling and inducing disordered glycolysis and pathological proliferation in pulmonary artery endothelial cells (PAECs) [1, 8]. Experimental evidence suggests that inhibiting tsRNA-3040b can restore Trim35 levels, normalize glucose metabolism, and alleviate the progression of PH in animal models [3, 6]. Consequently, tsRNA-3040b is recognized as a promising therapeutic target and a potential diagnostic biomarker for pulmonary vascular diseases [4, 5].

Other names

tsRNA-Asp-GTC-3040btRNA-derived fragment 3040btRF-3040b

Inhibition of tsRNA-3040b using antisense oligonucleotides or specific inhibitors to prevent R-loop formation at the Trim35 locus, thereby restoring Trim35 expression and normalizing glucose metabolism.