RNA binding proteins drive proliferation and tumorigenesis by regulating the translation and stability of specific subsets of mRNAs. We have investigated the role of eIF4B in this process and identify 10-fold more RNA binding sites for eIF4B in tumour cells from patients with diffuse large B-cell lymphoma compared to control B cells and, using iCLIP, find that eIF4B binds the entire length of mRNA transcripts. eIF4B stimulates the helicase activity of eIF4A thereby promoting the unwinding of RNA structure within the 5’ UTRS of mRNAs. We have found that, in addition to its well-documented role in mRNA translation, eIF4B additionally interacts with proteins associated with RNA turnover, including UPF1, which plays a key role in histone mRNA degradation at the end of S-phase. Consistent with these data we locate an eIF4B binding site upstream of the stem loop structure in histone mRNAs and show that decreased eIF4B expression alters histone mRNA turnover and delays cell cycle progression through S-phase. Collectively these data provide insight into how eIF4B promotes tumorigenesis.
