RNA seq of SiHa WT vs IFITM1/3 KO

IFITM proteins play a role in cancer cell progression through
undefined mechanisms. Here, we propose an emergent role of
IFITM1/3 regulating protein synthesis. SBP tagged IFITM1 protein
was used to identify an association of IFITM1 protein with the
cytosolic isoform of SRSF1 that transports mRNA to the ribosome.
This cytosolic association was confirmed in situ using proximity
ligation assays for SRSF1 and IFITM1/3, suggesting a role associated with
translation. Accordingly, IFITM1/3 were shown to interact with HLA-B mRNA
in response to IFNγ stimulation using RNA-protein proximity ligation
assays. In addition, shotgun RNA sequencing in IFITM1/IFITM3 null cells
and wt-SiHa cells indicated that reduced HLA-B gene expression does
not account for lowered HLA-B protein synthesis in response to
IFNγ. Furthermore, ribosome profiling using sucrose gradient sedimentation
identified a reduction in 80S ribosomal fraction an IFITM1/IFITM3
null cells compared to their wild-type counterpart, partially reverted by
IFITM1/3 complementation. Our data all together link the binding
of IFITM1/3 proteins to HLA-B mRNA and SRSF1 as a mechanism to
catalyze the synthesis of target proteins, suggesting an RNA
chaperonin role for IFITM1/3 proteins.