hnRNP A/B Proteins: An Encyclopedic Assessment of Their Roles in Homeostasis and Disease

SIMPLE SUMMARY: The hnRNP A/B family of proteins (comprised of A1, A2/B1, A3, and A0) contributes to the regulation of the majority of cellular RNAs. Here, we provide a comprehensive overview of what is known of each protein’s functions, highlighting important differences between them. While there is extensive information about A1 and A2/B1, we found that even the basic functions of the A0 and A3 proteins have not been well-studied. We also noted that the regulation and tissue distribution of all four of the proteins and their different isoforms require further study. Finally, since these proteins together play such a central role in regulating the cell’s RNA, we call for careful comparative examination of these proteins to better define the precise boundaries of each protein’s role in cell function and disease. ABSTRACT: The hnRNP A/B family of proteins is canonically central to cellular RNA metabolism, but due to their highly conserved nature, the functional differences between hnRNP A1, A2/B1, A0, and A3 are often overlooked. In this review, we explore and identify the shared and disparate homeostatic and disease-related functions of the hnRNP A/B family proteins, highlighting areas where the proteins have not been clearly differentiated. Herein, we provide a comprehensive assembly of the literature on these proteins. We find that there are critical gaps in our grasp of A/B proteins’ alternative splice isoforms, structures, regulation, and tissue and cell-type-specific functions, and propose that future mechanistic research integrating multiple A/B proteins will significantly improve our understanding of how this essential protein family contributes to cell homeostasis and disease.