Changed in translation: mRNA recoding by −1 programmed ribosomal frameshifting

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Highlights

•

–1PRF occurs when ribosomes move over a slippery sequence.
•

A frameshifting pseudoknot/stem-loop element stalls ribosomes in a metastable state.
•

–1PRF may contribute to the quality-control machinery in eukaryotes.
•

Trans-acting factors (proteins, miRNAs, or antibiotics) can modulate –1PRF.

Abstract

Programmed −1 ribosomal frameshifting (−1PRF) is an mRNA recoding event commonly utilized by viruses and bacteria to increase the information content of their genomes. Recent results have implicated −1PRF in quality control of mRNA and DNA stability in eukaryotes. Biophysical experiments demonstrated that the ribosome changes the reading frame while attempting to move over a slippery sequence of the mRNA – when a roadblock formed by a folded downstream segment in the mRNA stalls the ribosome in a metastable conformational state. The efficiency of −1PRF is modulated not only by cis-regulatory elements in the mRNA but also by trans-acting factors such as proteins, miRNAs, and antibiotics. These recent results suggest a molecular mechanism and new important cellular roles for −1PRF.

Related collections

Most cited references 73

Record: found
Abstract: found
Article: not found

The evolutionary consequences of erroneous protein synthesis.

D. Drummond, Claus Wilke (2009)

Errors in protein synthesis disrupt cellular fitness, cause disease phenotypes and shape gene and genome evolution. Experimental and theoretical results on this topic have accumulated rapidly in disparate fields, such as neurobiology, protein biosynthesis and degradation and molecular evolution, but with limited communication among disciplines. Here, we review studies of error frequencies, the cellular and organismal consequences of errors and the attendant long-range evolutionary responses to errors. We emphasize major areas in which little is known, such as the failure rates of protein folding, in addition to areas in which technological innovations may enable imminent gains, such as the elucidation of translational missense error frequencies. Evolutionary responses to errors fall into two broad categories: adaptations that minimize errors and their attendant costs and adaptations that exploit errors for the organism's benefit.

0 comments Cited 200 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Following translation by single ribosomes one codon at a time.

H F Noller, Ana Carolina de Mattos Zeri, Carlos Bustamante … (2008)

We have followed individual ribosomes as they translate single messenger RNA hairpins tethered by the ends to optical tweezers. Here we reveal that translation occurs through successive translocation--and-pause cycles. The distribution of pause lengths, with a median of 2.8 s, indicates that at least two rate-determining processes control each pause. Each translocation step measures three bases--one codon-and occurs in less than 0.1 s. Analysis of the times required for translocation reveals, surprisingly, that there are three substeps in each step. Pause lengths, and thus the overall rate of translation, depend on the secondary structure of the mRNA; the applied force destabilizes secondary structure and decreases pause durations, but does not affect translocation times. Translocation and RNA unwinding are strictly coupled ribosomal functions.

0 comments Cited 159 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Efficient -2 frameshifting by mammalian ribosomes to synthesize an additional arterivirus protein.

Eric Snijder, M A Taş, Hinke van der Weide … (2012)

Programmed -1 ribosomal frameshifting (-1 PRF) is a gene-expression mechanism used to express many viral and some cellular genes. In contrast, efficient natural utilization of -2 PRF has not been demonstrated previously in eukaryotic systems. Like all nidoviruses, members of the Arteriviridae (a family of positive-stranded RNA viruses) express their replicase polyproteins pp1a and pp1ab from two long ORFs (1a and 1b), where synthesis of pp1ab depends on -1 PRF. These polyproteins are posttranslationally cleaved into at least 13 functional nonstructural proteins. Here we report that porcine reproductive and respiratory syndrome virus (PRRSV), and apparently most other arteriviruses, use an additional PRF mechanism to access a conserved alternative ORF that overlaps the nsp2-encoding region of ORF1a in the +1 frame. We show here that this ORF is translated via -2 PRF at a conserved G_GUU_UUU sequence (underscores separate ORF1a codons) at an estimated efficiency of around 20%, yielding a transframe fusion (nsp2TF) with the N-terminal two thirds of nsp2. Expression of nsp2TF in PRRSV-infected cells was verified using specific Abs, and the site and direction of frameshifting were determined via mass spectrometric analysis of nsp2TF. Further, mutagenesis showed that the frameshift site and an unusual frameshift-stimulatory element (a conserved CCCANCUCC motif 11 nucleotides downstream) are required to direct efficient -2 PRF. Mutations preventing nsp2TF expression impair PRRSV replication and produce a small-plaque phenotype. Our findings demonstrate that -2 PRF is a functional gene-expression mechanism in eukaryotes and add another layer to the complexity of arterivirus genome expression.

0 comments Cited 120 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Marina V. Rodnina

Journal

Journal ID (nlm-ta): Trends Biochem Sci

Journal ID (iso-abbrev): Trends Biochem. Sci

Title: Trends in Biochemical Sciences

Publisher: Elsevier Ltd.

ISSN (Print): 0968-0004

ISSN (Electronic): 0968-0004

Publication date PMC-release: 4 April 2015

Publication date (Print): May 2015

Publication date (Electronic): 4 April 2015

Volume: 40

Issue: 5

Pages: 265-274

Affiliations

[0005]Department of Physical Biochemistry, Max Planck Institute for Biophysical Chemistry, 37077 Goettingen, Germany

Article

Publisher ID: S0968-0004(15)00044-4

DOI: 10.1016/j.tibs.2015.03.006

PMC ID: 7126180

PubMed ID: 25850333

SO-VID: df2ffa55-a1c3-4bc1-a5e6-c35706a3d282

License:

Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

Changed in translation: mRNA recoding by −1 programmed ribosomal frameshifting

Read this article at

Highlights

Abstract

Related collections

Journal of Circulating Biomarkers

Most cited references 73

The evolutionary consequences of erroneous protein synthesis.

Following translation by single ribosomes one codon at a time.

Efficient -2 frameshifting by mammalian ribosomes to synthesize an additional arterivirus protein.

Author and article information

Contributors

Journal

Affiliations

Article

History

Categories

Comments

Comment on this article

Similar content 56

Cited by 60

Most referenced authors 488