LAUSR

Modularity provides proteins versatility in regulating many cellular processes. The RNA Recognition Motif (RRM) is a common protein family that adopts modularity to facilitate its biological activity. hnRNP H contains three RRMs that play important roles in RNA splicing by binding G-rich enhancer element2. However, the mechanism three RRMs use to recognize RNA is still unknown. Here, based on the analysis of paramagnetic relaxation enhancement (PRE), the data indicates that hnRNP H RRM12 adopts a closed conformation in the absence of RNA. Second, dynamics experiments, T1, T2 and NOE also reveals that RRM1 and RRM2 domain share similar motion, which suggests that compact (closed) form is major population in solution. Moreover, in closed form, one of two bindings site was buried in compact structure. Based on above observation, we propose a hypothesis that there is chemical equilibrium between open form and close form. Once hnRNP H recognizes its G-rich binding sequencing, it will release the blocking RRM from closed form and reestablish chemical equilibrium toward to open form through conformational selection in presence of RNA3. Integrated methods like NMR paramagnetic relaxation enhancement, dynamics experiments and SAXS would be utilized to address this hypothesis.