The ribosome uses two active mechanisms to unwind messenger RNA during translation
Journal
Nature
Journal Volume
475
Journal Issue
7354
Pages
118 - 121
Date Issued
2011
Author(s)
Abstract
The ribosome translates the genetic information encoded in messenger RNA into protein. Folded structures in the coding region of an mRNA represent a kinetic barrier that lowers the peptide elongation rate, as the ribosome must disrupt structures it encounters in the mRNA at its entry site to allow translocation to the next codon. Such structures are exploited by the cell to create diverse strategies for translation regulation, such as programmed frameshifting, the modulation of protein expression levels, ribosome localization and co-translational protein folding. Although strand separation activity is inherent to the ribosome, requiring no exogenous helicases, its mechanism is still unknown. Here, using a single-molecule optical tweezers assay on mRNA hairpins, we find that the translation rate of identical codons at the decoding centre is greatly influenced by the GC content of folded structures at the mRNA entry site. Furthermore, force applied to the ends of the hairpin to favour its unfolding significantly speeds translation. Quantitative analysis of the force dependence of its helicase activity reveals that the ribosome, unlike previously studied helicases, uses two distinct active mechanisms to unwind mRNA structure: it destabilizes the helical junction at the mRNA entry site by biasing its thermal fluctuations towards the open state, increasing the probability of the ribosome translocating unhindered; and it mechanically pulls apart the mRNA single strands of the closed junction during the conformational changes that accompany ribosome translocation. The second of these mechanisms ensures a minimal basal rate of translation in the cell; specialized, mechanically stable structures are required to stall the ribosome temporarily. Our results establish a quantitative mechanical basis for understanding the mechanism of regulation of the elongation rate of translation by structured mRNAs. ? 2011 Macmillan Publishers Limited. All rights reserved.
SDGs
Other Subjects
messenger RNA; transfer RNA; enzyme activity; gene expression; molecular analysis; peptide; quantitative analysis; RNA; translocation; article; molecular model; priority journal; protein folding; ribosome; RNA sequence; RNA structure; RNA translation; translation regulation; Base Pairing; Base Sequence; Codon; GC Rich Sequence; HIV Reverse Transcriptase; Models, Molecular; Molecular Sequence Data; Nucleic Acid Conformation; Optical Tweezers; Peptide Chain Elongation, Translational; Protein Biosynthesis; Ribosomes; RNA Helicases; RNA, Messenger; Thermodynamics
Type
journal article