Ctu1-flox Mouse

Ctu1, part of the cytosolic thiouridylase complex with Ctu2, is crucial for the 2-thiolation at the 34th wobble uridine of the anticodon loop in specific tRNAs, such as tRNAGlnUUG, tRNAGluUUC, and tRNALysUUU [1,3]. This modification is essential for accurate mRNA decoding during translation and is involved in multiple biological processes, including angiogenesis, embryonic development, and maintaining genome integrity [1,3].

In zebrafish, deficiency of ctu1 leads to impaired angiogenesis and development, as well as cell cycle arrest, nerve development and erythrocyte differentiation defects, and attenuation of pro-angiogenic signaling pathways [1]. In melanoma cells, inhibition of CTU1 and/or CTU2, along with MAPK signalling, synergistically kills cells, and U34 enzymes like CTU1 promote glycolysis through codon-dependent regulation of HIF1A mRNA translation [2]. In breast cancer, up-regulation of CTU1/2 supports metastasis by promoting the translation of oncoprotein DEK and subsequent IRES-dependent translation of LEF1 [4]. In neuroblastoma, CTU1 is identified as a prognostic-related gene, and a risk model including CTU1 can predict patient survival [5].

In conclusion, Ctu1 plays essential roles in angiogenesis, embryonic development, and is associated with various diseases like melanoma, breast cancer, and neuroblastoma. Through model-based research, especially in zebrafish, its function in key biological processes and disease-related pathways has been revealed, providing insights into potential therapeutic strategies for these diseases.