tsRNA-3043a promotes apoptosis and senescence of ovarian granulosa cells to drive premature ovarian failure by targeting FLT1

Premature ovarian failure (POF) is the pathological aging of ovarian. The tRNA-derivedsmall fragments (tsRNAs) play important functions in diseases, however, whethertsRNAs participate in POF is still unclear. The cell and mice model of POF wereestablished, and tsRNAs profile in ovarian tissues of POF mice was revealed bysequencing. The function of tsRNA-3043a and its target gene FLT1 in POF cells andmice were detected. POF mice was characterized by decreased normal folliclenumber, ovarian weight, SOD level, and serum contents of E2, LH, and FSH. A total of81 tsRNAs were abnormally expressed in ovarian tissue of POF mice. The expressionof tsRNA-3043a was up-regulated in POF mice. tsRNA-3043a mimics inhibitedproliferation and promoted apoptosis, lipid accumulation, and cellular senescence ofovarian granulosa KGN cells, as well as altered transcriptome. tsRNA-3043a targetsbinding to the FLT1. Overexpression of FLT1 protected KGN cells from pathologicalaging. tsRNA-3043a promotes POF progression by inhibiting FLT1 in vitro and in vivo.tsRNA-3043a targeting inhibition of FLT1 to promote apoptosis and senescence ofovarian granulosa cells resulting in POF progression. This study provides a new targetfor pharmacological intervention in POF.