title: Structured mRNAs regulate translation initiation by binding to the platform of the ribosome.
abstract: 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.
authors: IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Department of Structural Biology and Genomics, Illkirch, F-67404 France.
authors: Stefano
authors: S
authors: Marzi
authors: Alexander G
authors: AG
authors: Myasnikov
authors: Alexander
authors: A
authors: Serganov
authors: Chantal
authors: C
authors: Ehresmann
authors: Pascale
authors: P
authors: Romby
authors: Marat
authors: M
authors: Yusupov
authors: Bruno P
authors: BP
authors: Klaholz
mesh_terms: D020121:5' Untranslated Regions; D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D020285:Cryoelectron Microscopy; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009690:Nucleic Acid Conformation; D010442:Peptide Chain Initiation, Translational; D011485:Protein Binding; D011487:Protein Conformation; D012329:RNA, Bacterial / Q000737:chemistry / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D012343:RNA, Transfer / Q000378:metabolism; D038621:Regulatory Sequences, Ribonucleic Acid; D012269:Ribosomal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012270:Ribosomes / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D040681:Structural Homology, Protein; D013997:Time Factors
chemical_list: D020121:5' Untranslated Regions; D029968:Escherichia coli Proteins; D012329:RNA, Bacterial; D012333:RNA, Messenger; D038621:Regulatory Sequences, Ribonucleic Acid; D012269:Ribosomal Proteins; C036004:ribosomal protein S15; D012343:RNA, Transfer