Background tRNA fragments (tRFs) are small non-coding RNAs generated from cleaved tRNA molecules, playing key roles in gene regulation and cellular processes. Produced by ribonucleases like angiogenin and Dicer, tRFs vary in length and function in gene silencing and stress responses. They interact with Argonaute proteins and affect mRNA levels, and are emerging as potential diagnostic and therapeutic targets for diseases such as cancer and neurodegenerative disorders. Given that the skin is the largest organ in mammals, it serves as an ideal model for studying development and various diseases. Therefore, this study investigates tRF expression in sheep skin tissues to understand their regulatory roles during growth and development.

Results This study analyzed skin tissue from five 1-month-old lambs and five 24-month-old adult Tan sheep using small RNA sequencing and proteomics. Raw sequencing data were filtered and aligned to identify various tsRNAs, while proteomic data were assessed for differential expression. Principal Component Analysis (PCA) revealed distinct separation between juvenile and adult samples based on tsRNA expression patterns, indicating intra-group similarity and inter-group differences. Differentially expressed tsRNAs were identified, with 19 highly expressed tsRNAs at 1 month of age. Proteomic screening identified 932 highly expressed and 835 lowly expressed proteins in the 1-month-old group, with functional enrichment highlighting immunity and inflammation pathways. Predictive analysis of tsRNA target genes intersected with 20 differentially expressed proteins involved in mitochondrial metabolism and stress response.

Conclusion This study reveals that tsRNAs significantly influence developmental and immune processes in sheep, with distinct expression patterns between juveniles and adults. Future research should validate these findings and fur ther elucidate the functional mechanisms of tsRNA regulation.