Characteristics of tRNA-Derived Small RNAs and microRNAs Associated with Immunocompromise in an Intrauterine Growth-Restricted Pig Model

SIMPLE SUMMARY: Intrauterine growth restriction (IUGR) refers to the slow growth and development of an embryo or fetus in the uterus of mammals. IUGR newborns commonly present with slow growth and the development of the body and organs accompany increased risks of infection during the early life period. IUGR remains a significant global public health issue, particularly in developing countries. In this work, we investigated the transfer RNA-derived small RNA and microRNA expression profiles in the spleen using pigs as an IUGR model. These results uncover an important potential regulator network involved in immunocompromise caused by IUGR. The present studies provide a novel perspective on the molecular regulatory mechanism of IUGR and a reference for prevention and treatment. ABSTRACT: Intrauterine growth restriction (IUGR) is an important cause of newborn morbidity and mortality in mammals. Transfer RNA-derived small RNA (tsRNA) has become an emerging non-coding RNA in recent years. tsRNA and microRNAs (miRNAs) share similar mechanisms, which are involved in various biological processes. In this study, the pig was used as a model of IUGR, and the tsRNA and miRNA expression profile in the spleen was characterized by RNA sequencing. A total of 361 miRNAs and 620 tsRNAs were identified, of which 22 were differentially expressed miRNA (DEM) and 25 differentially expressed tsRNA (DET). tRF-5c were the primary tsRNA type making up more than 90%, and the most abundantly expressed tsRNAs are from tRNA-Gly-GCC. Functional enrichment analysis found that those DETs and DEMs have been implicated in the immune system process. Protein–protein interaction (PPI) network analysis revealed ssc-miR-370, ssc-miR-206, tiRNA-Ser-TGA-001 and tRF-Val-AAC-034 could be major regulators. TNF, TLR4, CD44, MAPK1 and STAT1 were predicted hub target genes. Those DETs and DEMs may regulate the T-cell receptor signaling pathway and Toll-like receptor signaling pathway to mediate the immunocompromise caused by IUGR. The results discussed in this article uncover the potential role of tsRNAs and miRNAs in IUGR porcine spleen.