Tumor suppressor RBM5 directly interacts with the DExD/H-box protein DHX15 and stimulates its helicase activity

RNA binding motif protein 5 (RBM5) is a candidate tumor suppressor gene. Recent studies showed that RBM5 functions as an alternative splicing regulator of apoptosis-related genes. Here, we identify DHX15 and PRP19, two spliceosome components, as novel RBM5-interacting partners. We then show that the G-patch domain of RBM5 is indispensable for its ability to interact with DHX15. Strikingly, we find that RBM5 stimulates the helicase activity of DHX15 in a G patch domain-dependent manner in vitro. Helicase activities play critical roles in modulating pre-mRNA splicing. Our findings thus suggest a new mechanism underlying the regulatory roles of RBM5 in pre-mRNA splicing.Structured summary of protein interactionsDHX15physically interacts with RBM5 by anti tag coimmunoprecipitation (View Interaction: 1, 2, 3, 4, 5, 6, 7).RBM5binds to PRP19 by pull down (View Interaction: 1, 2)RBM5binds to DHX15 by pull down (View Interaction: 1, 2)DHX15physically interacts with RBM5 by two hybrid (View interaction)PRP19physically interacts with RBM5 by anti tag coimmunoprecipitation (View Interaction: 1, 2)RBM5binds to U2AF65 by pull down (View interaction)RBM5physically interacts with DHX15, PRP19, PRPF8 and SNRNP200 by anti tag coimmunoprecipitation (View interaction)RBM5physically interacts with DHX15, PRP19 and U2AF65 by anti bait coimmunoprecipitation (View interaction)

► We identify DHX15 and PRP19, two splicing factors, as new RBM5-associated partners. ► RBM5 directly interacts with DHX15 through its carboxyl (C)-terminal G-patch domain. ► DHX15 has an ATP-dependent helicase activity. ► RBM5 stimulates the helicase activity of DHX15 by its G-patch domain.