Structured mRNAs Regulate Translation Initiation by Binding to the Platform of the Ribosome

• Published in: Cell Vol. 130; no. 6; pp. 1019 - 1031
• Main Authors: Marzi, Stefano, Myasnikov, Alexander G., Serganov, Alexander, Ehresmann, Chantal, Romby, Pascale, Yusupov, Marat, Klaholz, Bruno P.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21-09-2007; Elsevier
• Subjects: 5' Untranslated Regions; Amino Acid Sequence; Base Sequence; Binding Sites; Cellular Biology; Cryoelectron Microscopy; Escherichia coli; Escherichia coli - genetics; Escherichia coli - metabolism; Escherichia coli Proteins; Escherichia coli Proteins - chemistry; Escherichia coli Proteins - genetics; Escherichia coli Proteins - metabolism; Gene Expression Regulation, Bacterial; Life Sciences; Models, Molecular; Molecular Sequence Data; Mutation; Nucleic Acid Conformation; Peptide Chain Initiation, Translational; Protein Binding; Protein Conformation; Regulatory Sequences, Ribonucleic Acid; Ribosomal Proteins; Ribosomal Proteins - chemistry; Ribosomal Proteins - genetics; Ribosomal Proteins - metabolism; Ribosomes; Ribosomes - chemistry; Ribosomes - metabolism; Ribosomes - ultrastructure; RNA; RNA, Bacterial; RNA, Bacterial - chemistry; RNA, Bacterial - metabolism; RNA, Messenger; RNA, Messenger - metabolism; RNA, Transfer; RNA, Transfer - metabolism; Sequence Homology, Amino Acid; Sequence Homology, Nucleic Acid; Structural Homology, Protein; Time Factors; RNA
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2007.07.008

Gene expression can be regulated at the level of initiation of protein biosynthesis via structural elements present at the 5′ untranslated region of mRNAs. These folded mRNA segments may bind to the ribosome, thus blocking translation until the mRNA unfolds. Here, we report a series of cryo-electron microscopy snapshots of ribosomal complexes directly visualizing either the mRNA structure blocked by repressor protein S15 or the unfolded, active mRNA. In the stalled state, the folded mRNA prevents the start codon from reaching the peptidyl-tRNA (P) site inside the ribosome. Upon repressor release, the mRNA unfolds and moves into the mRNA channel allowing translation initiation. A comparative structure and sequence analysis suggests the existence of a universal stand-by site on the ribosome (the 30S platform) dedicated for binding regulatory 5′ mRNA elements. Different types of mRNA structures may be accommodated during translation preinitiation and regulate gene expression by transiently stalling the ribosome.