A novel translational control mechanism involving RNA structures within coding sequences.
The impact of RNA structures in coding sequences (CDS) within mRNAs is poorly understood. Here, we identify a novel and highly conserved mechanism of translational control involving RNA structures within coding sequences and the DEAD-box helicase Dhh1. Using yeast genetics and genome-wide ribosome profiling analyses, we show that this mechanism, initially derived from studies of the Brome Mosaic virus RNA genome, extends to yeast and human mRNAs highly enriched in membrane and secreted proteins. All Dhh1-dependent mRNAs, viral and cellular, share key common features. First, they contain long and highly structured CDSs, including a region located around nucleotide 70 after the translation initiation site; second, they are directly bound by Dhh1 with a specific binding distribution; and third, complementary experimental approaches suggest that they are activated by Dhh1 at the translation initiation step. Our results show that ribosome translocation is not the only unwinding force of CDS and uncover a novel layer of translational control that involves RNA helicases and RNA folding within CDS providing novel opportunities for regulation of membrane and secretome proteins.
Molecular Virology Group, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain.
Jennifer
J
Jungfleisch
Max Planck Research Group for RNA Biology, Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany.|Cells-in-Motion Cluster of Excellence, University of Münster, 48149 Münster, Germany.
Danny D
DD
Nedialkova
Research Programme on Biomedical Informatics (GRIB), Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Hospital del Mar Medical Research Institute (IMIM), 08003 Barcelona, Spain.
Ivan
I
Dotu
Institute for Molecular Biology, Göttingen University Medical Department, 37073 Göttingen, Germany.
Katherine E
KE
Sloan
Program of Cancer Research, Hospital del Mar Medical Research Institute (IMIM), 08003 Barcelona, Spain.
Neus
N
Martinez-Bosch
Institute for Molecular Biology, Göttingen University Medical Department, 37073 Göttingen, Germany.
Lukas
L
Brüning
Statistical Genomics, Centro Nacional de Analisis Genomica, 08028 Barcelona, Spain.
Emanuele
E
Raineri
Program of Cancer Research, Hospital del Mar Medical Research Institute (IMIM), 08003 Barcelona, Spain.
Pilar
P
Navarro
Institute for Molecular Biology, Göttingen University Medical Department, 37073 Göttingen, Germany.|Göttingen Center for Molecular Biosciences, Georg-August University, 37073 Göttingen, Germany.
Markus T
MT
Bohnsack
Max Planck Research Group for RNA Biology, Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany.|Cells-in-Motion Cluster of Excellence, University of Münster, 48149 Münster, Germany.|Faculty of Medicine, University of Münster, 48149 Münster, Germany.
Sebastian A
SA
Leidel
Molecular Virology Group, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain.
Juana
J
Díez
D017795:Bromovirus / Q000235:genetics; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D009690:Nucleic Acid Conformation; D016366:Open Reading Frames / Q000235:genetics; D010442:Peptide Chain Initiation, Translational; D014176:Protein Biosynthesis; D012313:RNA / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012270:Ribosomes / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*
D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D012313:RNA; C445083:DHH1 protein, S cerevisiae; D053487:DEAD-box RNA Helicases