YRDC, or yrdC N6 -threonylcarbamoltransferase domain containing protein, is a crucial enzyme for the formation of N6 -threonylcarbamoyladenosine (t6A) on ANN -decoding tRNA species [1,6]. This modification is essential for accurate and efficient translation, ensuring proper recognition of ANN codons, increasing codon affinity, and enhancing ribosome binding [6]. YRDC is associated with pathways like the RAS/RAF/MEK/ERK pathway [2], and its function impacts various biological processes such as cell proliferation, apoptosis, and genomic stability [3,4,5]. Genetic models, such as gene knockout (KO) and conditional knockout (CKO) mouse models, can be valuable for studying YRDC's function.

Knockdown of YRDC in glioblastoma stem cells (GSCs) reduced t6A formation, suppressed global translation, and inhibited tumor growth both in vitro and in vivo [1]. In hepatocarcinoma cells, YRDC knockdown decreased susceptibility to lenvatinib, and it was found to regulate the protein translation of KRAS [2]. In non -small cell lung cancer (NSCLC) cell lines, YRDC knockdown significantly suppressed cell growth, colony formation, and induced apoptosis [3]. In hepatocellular carcinoma cells, YRDC depletion suppressed proliferation, migration, and invasion [4]. In a patient with a severe neonatal progeroid phenotype, a novel homozygous missense mutation in YRDC impaired its function, resulting in reduced t6A modifications of tRNAs, telomere shortening, and DNA repair defects [5].

In conclusion, YRDC plays a vital role in tRNA modification, which is essential for accurate translation. Model -based research, especially through KO/CKO mouse models, has revealed its significance in cancer development, including glioblastoma, hepatocarcinoma, and NSCLC. Additionally, YRDC mutations are associated with a developmental disorder with progeroid features, highlighting its importance in genomic stability and normal development [1,2,3,4,5].