Structural analysis of cooperative RNA binding by the La motif and central RRM domain of human La protein

Abstract

The La protein is a conserved component of eukaryotic ribonucleoprotein complexes that binds the 3' poly(U)-rich elements of nascent RNA polymerase III (pol III) transcripts to assist folding and maturation. This specific recognition is mediated by the N-terminal domain (NTD) of La, which comprises a La motif and an RNA recognition motif (RRM). We have determined the solution structures of both domains and show that the La motif adopts an alpha/beta fold that comprises a winged-helix motif elaborated by the insertion of three helices. Chemical shift mapping experiments show that these insertions are involved in RNA interactions. They further delineate a distinct surface patch on each domain-containing both basic and aromatic residues-that interacts with RNA and accounts for the cooperative binding of short oligonucleotides exhibited by the La NTD.