The conserved wobble uridine tRNA thiolase Ctu1 is required to sustain development and differentiation

Abstract

Recent studies have revealed that tRNA modification is an important epigenetic mechanism involved in gene expression. Cytosolic thiouridylase (consisting of Ctu1 and Ctu2 subunit) are the enzyme complex which catalyze the thio-modification at the 34th wobble uridine of the anticodon of tRNAGlnUUG, tRNAGluUUC, and tRNALysUUU. Besides introducing a thiol group at the C2 positions, those tRNAs were commonly modified with a methoxycarbonylmethyl at the C5 positions by Elongator and ALKBH8. tRNA-U34 modification, particularly the Elongator and ALKBH8, has been demonstrated to be involved in disease and development, however, the biological functional level of CTU in vertebrates remains elusive. Here, we found that in zebrafish, CTU may be an important regulatory factor in development and erythroid differentiation. By using morpholino targeting and knocking down CTU1, we observed that the loss of CTU1 led to impaired zebrafish larval development and blood vessel formation. Single-cell sequencing analysis showed that erythroid cell differentiation in the CTU1 knockdown group was blocked at an early stage, while the wild-type group exhibited mature erythroid cells. These findings suggest that CTU1 is involved in regulating erythrocyte development. These findings provide new insights into the biological function of CTU1.