Profile of tRNA-derived short non-coding RNAs during monocyte differentiation and their role in macrophage survival

Monocytes, a type of leukocytes, are key players in immune responses, transitioning to macrophages at infection sites. Differentiation, which is crucial for macrophage survival and resistance to apoptosis, is a tightly regulated process. Based on our earlier findings implicating the 5'-fragment of tRNA^HisGUG (5'-HisGUG) in macrophage biology, we specifically focused on these fragments to investigate its regulation during monocyte-to-macrophage differentiation and its role in macrophage survival. We performed small RNA sequencing during monocyte-to-macrophage differentiation using THP-1 cells and identified 5'-HisGUG as a prominently regulated tDR. Notably, transfection of 5'-HisGUG in macrophages decreased survival under apoptotic stress. We propose that 5'-HisGUG can also act as an obstructive RNA (oRNA), and its reduction is critical for macrophage survival under stress.