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.

The La protein is an important component of ribonucleoprotein complexes that acts mainly as an RNA chaperone to facilitate correct processing and maturation of RNA polymerase III transcripts, but can also stimulate translation initiation. We report here the structure of the C-terminal domain of human La, which comprises an atypical RNA recognition motif (La225-334) and a long unstructured C-terminal tail. The central beta sheet of La225-334 reveals novel features: the putative RNA binding surface is formed by a five-stranded beta sheet and, strikingly, is largely obscured by a long C-terminal alpha helix that encompasses a recently identified nuclear retention element. Contrary to previous observations, we find that the La protein does not contain a dimerization domain.

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