Ctu1-KO Mouse

Ctu1, a subunit of cytosolic thiouridylase, is crucial for the 2-thiolation at the 34th wobble uridine of the anticodon loop of specific tRNAs, such as tRNAGlnUUG, tRNAGluUUC, and tRNALysUUU [2,3,5]. This modification is involved in proper mRNA decoding by the ribosome, influencing translation fidelity and playing a role in pathways related to cell cycle regulation, development, and disease [2,3].

In zebrafish, deficiency of ctu1 leads to impaired angiogenesis and embryonic development, with single-cell RNA sequencing revealing cell cycle arrest, nerve development and erythrocyte differentiation defects, and attenuation of pro-angiogenic signaling pathways [2]. In nematode and fission yeast, inactivation of the Ctu1-Ctu2 complex results in loss of tRNA thiolation, thermosensitive viability decrease, ploidy abnormalities, and aberrant development, suggesting a role in maintaining genome integrity [3]. In human melanoma cells, inhibition of CTU1, along with ELP3 or CTU2, can synergize with MAPK signalling inhibition to kill cells, indicating its importance in cancer cell survival and resistance to targeted therapy [1]. In breast cancer, up-regulation of CTU1/2 sustains metastasis by supporting the translation of oncoproteins [4]. In neuroblastoma, CTU1 is identified as a prognostic-related gene, and a prognostic risk score model including CTU1 shows predictive value for patient survival [6]. In cattle, a missense variant in CTU1 may impact direct calving difficulty [7].

In summary, Ctu1 is essential for angiogenesis, embryonic development, genome integrity, and has implications in cancer and other diseases. Studies using genetic models like zebrafish, nematode, fission yeast, and in human cell lines have revealed its role in these biological processes and disease conditions, providing insights into potential therapeutic targets and prognostic markers.