Biochemistry Seminar
"Thermodynamic Coupling of the Tandem RRM Domains of hnRNP A1 Underlie its Pleiotropic RNA Binding Functions”
Zoom Link:
https://mtsu.zoom.us/j/3467792052?pwd=I4tKcqFvCJuUTmwQNz3GR2iBOG6SoD.1&omn=83556292248
Meeting ID: 346 779 2052
Password: 237846
Abstract: In order to regulate their varied RNA-Protein and Protein-Protein interactions, RNA binding proteins (RBPs) utilize allosteric interdomain interactions. However, there have been few studies to investigate the biophysical properties that underlie this phenomenon. hnRNP A1 serves as the model protein for this work and contains two RNA recognition motifs (RRMs) within its amino-terminal domain. Here these RRMs are shown to have vastly different stabilities and interdomain communication between RRM1 and RRM2 is critical for the stability of the full-length protein. 15N Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion experiments were used to evaluate the differential conformational fluctuations of RRMs 1 and 2. Additionally, high pressure solution NMR was employed to probe the unfolding dynamics of the wild type hnRNP A1 and a series of mutant constructs from which it was determined that interdomain communication between RRM1 and RRM2 stabilizes the two domains in high-pressure conditions. In vivo CLIP-seq experiments also show that disruption of interdomain communication significantly altered the RNA binding ability of hnRNP A1. This work reveals the role of allostery in the regulatory capacity of hnRNP A1 as it interacts with many different RNA targets and suggests that this mode of regulation could be utilized by many other RBPs to hone their RNA binding interactions.
Citation: Jeffrey D. Levengood et al., Thermodynamic coupling of the tandem RRM domains of hnRNP A1 underlie its pleiotropic RNA binding functions.Sci. Adv.10,eadk6580(2024).DOI:10.1126/sciadv.adk6580