Structural insight into functional aspects of ribosomal RNA targeting.

Abstract

Ribosomes are giant riboprotein assemblies that play the main role in the translation of the genetic code into proteins. All ribosomes consist of two subunits of unequal size with defined tasks. The small ribosomal subunit is involved in the initiation of the translation process, in choosing the translated frame, in decoding the genetic message, and in controlling the fidelity of codon± anticodon interactions. The large subunit catalyzes the formation of the peptide bond and gates the nascent chains by channeling them through their dynamic exit tunnel. Messenger RNA (mRNA) and tRNA carry the genetic information and the amino acids, respectively. The ribosome possesses a channel along which the mRNA chain progresses and three tRNA binding sites, designated as A (aminoacyl), P (peptidyl), and E (exit). All tRNA molecules are built primarily of double helices, with an anticodon stem loop at one end and a single-stranded CCA moiety on their other end. The amino acids to be incorporated in the nascent proteins and the newly formed polypeptide chains bind to the CCA end. The mRNA and the anticodon loop of the tRNA molecules interact with the small subunit, whereas the acceptor stem and the 3 end of the tRNA molecules bind to the large subunit. Hence, each of the three tRNA molecules is located on both subunits, which act in concert during the elongation cycle in order to translocate the Aand P-tRNA molecules together with the mRNA by precisely one codon. Recently obtained crystal structures of ribosomal particles showed unambiguously that both ribosomal active sites, namely the decoding and peptidyl transferase centers, consist exclusively of ribosomal RNA (rRNA). As the primary actor in the process of protein biosynthesis, the ribosomal RNA is targeted by substrates, by nonribosomal factors participating in the process, and by antibiotics and inhibitors. Many clinically relevant antibiotics hamper ribosomal functions by binding primarily to ribosomal RNA. Self-rRNA targeting plays a major role in the creation of functional ribosomes. This article highlights recent advances in studies aimed at the understanding of the molecular mechanisms that are triggered, accomplished, or assisted by rRNA interactions.