A NUCLEAR-LOCALIZATION DOMAIN IN THE HNRNP A1 PROTEIN

The heterogeneous nuclear RNP (hnRNP) A1 protein is one of the major p re-mRNA/mRNA binding proteins in eukaryotic cells and one of the most abundant proteins in the nucleus. It is localized to the nucleoplasm a nd it also shuttles between the nucleus and the cytoplasm. The amino a cid sequence of A1 contains two RNP motif RNA-binding domains (RBDs) a t the amino terminus and a glycine-rich domain at the carboxyl terminu s. This configuration, designated 2 x RBD-Gly, is representative of pe rhaps the largest family of hnRNP proteins. Unlike most nuclear protei ns characterized so far, A1 (and most 2 x RBD-Gly proteins) does not c ontain a recognizable nuclear localization signal (NLS). We have found that a segment of ca. 40 amino acids near the carboxyl end of the pro tein (designated MB) is necessary and sufficient for nuclear localizat ion; attaching this segment to the bacterial protein beta-galactosidas e or to pyruvate kinase completely localized these otherwise cytoplasm ic proteins to the nucleus. The RBDs and another RNA binding motif fou nd in the glycine-rich domain, the RGG box, are not required for A1 nu clear localization. M9 is a novel type of nuclear, localization domain as it does not contain sequences similar to classical basic-type NLS. Interestingly, sequences similar to MB are found in other nuclear RNA -binding proteins including hnRNP A2.