Structured mRNAs regulate translation initiation by binding to the platform of the ribosome

Stefano Marzi; Alexander G Myasnikov; Alexander Serganov; Chantal Ehresmann; Pascale Romby; Marat Yusupov; Bruno P Klaholz

doi:10.1016/j.cell.2007.07.008

Structured mRNAs regulate translation initiation by binding to the platform of the ribosome

Cell. 2007 Sep 21;130(6):1019-31. doi: 10.1016/j.cell.2007.07.008.

Authors

Stefano Marzi¹, Alexander G Myasnikov, Alexander Serganov, Chantal Ehresmann, Pascale Romby, Marat Yusupov, Bruno P Klaholz

Affiliation

¹ IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Department of Structural Biology and Genomics, Illkirch, F-67404 France.

PMID: 17889647
DOI: 10.1016/j.cell.2007.07.008

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.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

5' Untranslated Regions
Amino Acid Sequence
Base Sequence
Binding Sites
Cryoelectron Microscopy
Escherichia coli / genetics*
Escherichia coli / metabolism
Escherichia coli Proteins / chemistry
Escherichia coli Proteins / genetics
Escherichia coli Proteins / metabolism*
Gene Expression Regulation, Bacterial*
Models, Molecular
Molecular Sequence Data
Mutation
Nucleic Acid Conformation
Peptide Chain Initiation, Translational*
Protein Binding
Protein Conformation
RNA, Bacterial / chemistry
RNA, Bacterial / metabolism*
RNA, Messenger / metabolism*
RNA, Transfer / metabolism
Regulatory Sequences, Ribonucleic Acid
Ribosomal Proteins / chemistry
Ribosomal Proteins / genetics
Ribosomal Proteins / metabolism*
Ribosomes / chemistry
Ribosomes / metabolism*
Ribosomes / ultrastructure
Sequence Homology, Amino Acid
Sequence Homology, Nucleic Acid
Structural Homology, Protein
Time Factors

Substances

5' Untranslated Regions
Escherichia coli Proteins
RNA, Bacterial
RNA, Messenger
Regulatory Sequences, Ribonucleic Acid
Ribosomal Proteins
ribosomal protein S15
RNA, Transfer

Associated data

PDB/2VAZ