Investigating SAMD9/9L Activity in Cellular Defense and Growth Control

The sterile alpha motif domain-containing 9 (SAMD9) and SAMD9-like (SAMD9L) (SAMD9/9L) are evolutionary-conserved genes whose expression was stimulated by interferons. They have been implicated in immune responses to viral pathogens and are associated with an increased risk of developing myeloid malignancies. This degree project aims to investigate the molecular mechanisms involved in the activation and regulation of SAMD9/9L, as well as the pathogenesis caused by pathogenic variants in these genes. We first knocked out CAPRIN1, a stress granule-associated component that potentially interacts with SAMD9/9L, in both wild-type (WT) and SAMD9/9L double knockout (DKO) monocytic THP-1 cells. We then determined whether sodium arsenite-induced stress triggers SAMD9/9L activation and assessed the effect of CAPRIN1 on SAMD9/9L activation under stress conditions using L-homopropargylglycine (HPG) protein synthesis assays. Additionally, we examined the signaling pathways that govern the formation of stalled pre-initiation complexes (PICs) associated with SAMD9/9L-mediated stress granule (SG) induction; our results showed that there were no significant differences between WT and SAMD9/9L DKO HeLa cells, suggesting that SAMD9/9L may not be involved in the signaling pathway of stress granule formation.