HUMAN HNRNP PROTEIN A1 - A MODEL POLYPEPTIDE FOR A STRUCTURAL AND GENETIC INVESTIGATION OF A BROAD FAMILY OF RNA-BINDING PROTEINS

The hnRNP fiber is the substrate on which pre-mRNA processing occurs. The protein moiety of the fiber (hnRNP proteins) constitutes a broad f amily of RNA binding proteins that revealed, upon molecular analysis, a number of interesting features. Heterogeneous nuclear ribonucleoprot ein A1 is a major component of the human hnRNP complex. In recent year s this protein has attracted great attention because of several emergi ng evidences of its direct involvement in pre-mRNA processing and it h as become one of the best characterized RNA binding proteins. Detailed knowledge of the structure of protein A1 has laid the basis for the u nderstanding 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 th e binding properties of protein A1 as well as new data on the gene str ucture of A1 and of its closely related hnRNP protein A2. Our results show that a single Al molecule contains the determinants for simultane ous binding of two single-stranded nucleic acid molecules and we demon strate that the glycine-rich domain of A1, isolated from the rest of t he molecule, is capable of sustaining protein-protein interactions. Th ese features probably account for the reannealing activity of the prot ein and for its capacity to modulate the binding of snRNPs to intron s equences in vitro. Comparison of A1 and A2 gene sequences revealed a r emarkable conservation of the overall structural organization, suggest ing important functions for the different structural elements.