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Cell. 2015 Jun 4;161(6):1400-12. doi: 10.1016/j.cell.2015.05.008.

Widespread Co-translational RNA Decay Reveals Ribosome Dynamics.

Author information

1
European Molecular Biology Laboratory (EMBL), Genome Biology Unit, 69117 Heidelberg, Germany.
2
Stanford Genome Technology Center, Stanford University, Palo Alto, CA 94304, USA; Department of Genetics, School of Medicine, Stanford University, Stanford, CA 94305, USA.
3
European Molecular Biology Laboratory (EMBL), Genome Biology Unit, 69117 Heidelberg, Germany; Stanford Genome Technology Center, Stanford University, Palo Alto, CA 94304, USA; Department of Genetics, School of Medicine, Stanford University, Stanford, CA 94305, USA. Electronic address: larsms@embl.de.

Abstract

It is generally assumed that mRNAs undergoing translation are protected from decay. Here, we show that mRNAs are, in fact, co-translationally degraded. This is a widespread and conserved process affecting most genes, where 5'-3' transcript degradation follows the last translating ribosome, producing an in vivo ribosomal footprint. By sequencing the ends of 5' phosphorylated mRNA degradation intermediates, we obtain a genome-wide drug-free measurement of ribosome dynamics. We identify general translation termination pauses in both normal and stress conditions. In addition, we describe novel codon-specific ribosomal pausing sites in response to oxidative stress that are dependent on the RNase Rny1. Our approach is simple and straightforward and does not require the use of translational inhibitors or in vitro RNA footprinting that can alter ribosome protection patterns.

PMID:
26046441
PMCID:
PMC4461875
DOI:
10.1016/j.cell.2015.05.008
[Indexed for MEDLINE]
Free PMC Article

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