Exploring The Cellular Function Of RBM24

RBM24 is an RNA-binding protein that is involved in the regulation of pre-mRNA splicing and stability,and plays an important role in cell fate determination.Previous studies found that RBM24 can specifically bind to the 3’-UTR region of target mRNA to regulate gene stability.For example,RBM24 regulates the expression of Myog,p21 and p53.Overexpression of RBM24 can increase the life of Myog and p21 in cells and decrease the expression of p53.In turn,knocking down Rbm24 decreases the life of Myog and p21,but increases the expression of p53.So far the study of RBM24 is mainly focused on the heart and muscle.Loss of RBM24 leads to impaired cardiac dysplasia and striated muscle differentiation in mice,probably due to the deletion of RBM24 leading to abnormal splicing of target mRNA in the heart and muscle.Our study found that RBM24 is highly expressed in vestibular systems and auditory hair cells in mice.This suggests that RBM24 may also play an important role in balance and hearing.RBM24,as an important RNA-binding protein,can interact with many different proteins in cells to perform different biological functions.To further explore the function of RBM24,yeast two-hybrid screening was used to find proteins that interact with it.The results showed that RBM38,RBFOX2 and GPATCH8 are the interacting proteins of RBM24.RBFOX2 is an RNA binding protein,which can not only participate in the regulation of splicing and stability of mRNAs,but also participate in the formation of Stress granules(SG).RBM24,as a multifunctional protein,can participate in the regulation of mRNAs stability in the cytoplasm and affect the splicing of pre-mRNA in the nucleus.In addition,previous studies found that some RNA-binding proteins,such as G3BP1 and TIA-1,can participate in the formation of stress granules.And our study also showed that overexpression of RBM24 could induce punctate aggregation in the cytoplasm just like stress granules.This suggests that RBM24 may be associated with stress granules.Stress granules are the dense particles formed in the cytoplasm by the aggregation of a series of proteins and the mRNA suspended in the cell during extreme environments,such as heat shock,viral infection,oxidative stress and arsenite.Stress granules are an adaptive regulatory mechanism produced by cells in the face of extreme environments.They are composed of a series of proteins and mRNAs.Therefore,one of the functions of stress granules is to store or release mRNAs,thereby regulating the translation of mRNAs.In addition,stress granules play an important role in many physiological and pathological processes,such as apoptosis,inflammatory responses,viral infection and neurodegenerative diseases.However,the mechanism of stress granules formation remains unclear.By treating cultured cells with stress conditions,we found that both endogenous and overexpressed RBM24 can enter the stress granules.And we also found that RBM24 can directly interact with G3BP1,the marker protein of SGs.Then using MEF cells of Rbm24-/-mice,we found that the formation of SGs is not significantly affected after the RBM24 protein was knocked out.Therefore,we speculated that RBM24 may be involved in the formation of SGs by binding to G3BP1,but is not essential for SG formation.However,due to time limit,we did not further study the mechanism of RBM24 regulating the formation of stress granules.In addition,which mRNAs can be brought into the SGs by RBM24?And which physiological functions can be affected under these conditions?These are questions which need to be further investigated.