Function of hnRNP A2 in neural cells

The amino acid sequence of the murine heterogeneous ribonucleoprotein (hnRNP) A2 is 99% homologous to that of human suggesting a conserved function. It consists of four functional domains: two sequential RNA binding domains (RBD) I and II, and a glycine-rich domain (GRD) continuous with a nuclear shuttling domain (M9). More than 90% of hnRNP A2 is found in the nucleus. In the cytoplasm, hnRNP A2 is present in complexes containing mRNAs. Individual domains of hnRNP A2 fused with green fluorescent protein were expressed in neural cells to determine their role in the intracellular distribution of hnRNP A2. Proteins containing the RBD II domain in combination with RBD I and/or GRD, and the one consisting solely of RBD II localize preferentially to the distal end of the cellular processes of oligodendrocytes (OLs). This pattern of distribution as well as that of endogenous hnRNP A2 requires intact microtubules. ^ M9 polypeptide binds to transportin, a protein necessary for nuclear import of hnRNP A2. Deletion of the M9 domain abolishes nuclear localization of hnRNP A2. However, both the GRD and M9 domain are necessary for import and/or retention in the nucleus of OLs. HnRNP A2 binds to a RNA sequence, A2RE, which is present is some mRNAs that are transported to the cell periphery. Addition of the A2RE oligonucleotide to the cell perikaryon specifically changes hnRNP A2 distribution from mainly nuclear to primarily cytoplasmic. Excess of A2RE oligonucleotide also interferes with the association of hnRNP A2 with transportin. These observations suggest that the intracellular distribution of hnRNP A2 depends on its interactions with several nuclear and cytoplasmic components, and that different interactions require specific domains of hnRNP A2.