Human hnRNP protein A1: a model polypeptide for a structural and genetic investigation of a broad family of RNA binding proteins.

Abstract

The hnRNP fiber is the substrate on which pre-mRNA processing occurs. The protein moiety of the fiber (hnRNP proteins) constitutes a broad family of RNA binding proteins that revealed, upon molecular analysis, a number of interesting features. Heterogeneous nuclear ribonucleoprotein A1 is a major component of the human hnRNP complex. In recent years this protein has attracted great attention because of several emerging evidences of its direct involvement in pre-mRNA processing and it has become one of the best characterized RNA binding proteins. Detailed knowledge of the structure of protein A1 has laid the basis for the understanding of its function, and for this reason A1 can be considered as a model polypeptide for the investigation of a large number of RNA binding proteins. In this work we report recent findings regarding the binding properties of protein A1 as well as new data on the gene structure of A1 and of its closely related hnRNP protein A2. Our results show that a single A1 molecule contains the determinants for simultaneous binding of two single-stranded nucleic acid molecules and we demonstrate that the glycine-rich domain of A1, isolated from the rest of the molecule, is capable of sustaining protein-protein interactions. These features probably account for the reannealing activity of the protein and for its capacity to modulate the binding of snRNPs to intron sequences in vitro. Comparison of A1 and A2 gene sequences revealed a remarkable conservation of the overall structural organization, suggesting important functions for the different structural elements.