Ribosome profiling reveals the role of yeast RNA-binding proteins Cth1 and Cth2 in translational regulation
Hanna Barlit,
Antonia M. Romero,
Ali Gülhan,
Praveen K. Patnaik,
Alexander Tyshkovskiy,
María T. Martínez-Pastor,
Vadim N. Gladyshev,
Sergi Puig,
Vyacheslav M. Labunskyy
Affiliations
Hanna Barlit
Department of Dermatology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA
Antonia M. Romero
Departamento de Biotecnología, Instituto de Agroquímica y Tecnología de Alimentos (IATA), Consejo Superior de Investigaciones Científicas (CSIC), Valencia, Spain
Ali Gülhan
Department of Dermatology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA
Praveen K. Patnaik
Department of Dermatology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA
Alexander Tyshkovskiy
Division of Genetics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
María T. Martínez-Pastor
Departamento de Biotecnología, Instituto de Agroquímica y Tecnología de Alimentos (IATA), Consejo Superior de Investigaciones Científicas (CSIC), Valencia, Spain; Departamento de Bioquímica y Biología Molecular, Universitat de València, Valencia, Spain
Vadim N. Gladyshev
Division of Genetics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
Sergi Puig
Departamento de Biotecnología, Instituto de Agroquímica y Tecnología de Alimentos (IATA), Consejo Superior de Investigaciones Científicas (CSIC), Valencia, Spain
Vyacheslav M. Labunskyy
Department of Dermatology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA; Corresponding author
Summary: Iron serves as a cofactor for enzymes involved in several steps of protein translation, but the control of translation during iron limitation is not understood at the molecular level. Here, we report a genome-wide analysis of protein translation in response to iron deficiency in yeast using ribosome profiling. We show that iron depletion affects global protein synthesis and leads to translational repression of multiple genes involved in iron-related processes. Furthermore, we demonstrate that the RNA-binding proteins Cth1 and Cth2 play a central role in this translational regulation by repressing the activity of the iron-dependent Rli1 ribosome recycling factor and inhibiting mitochondrial translation and heme biosynthesis. Additionally, we found that iron deficiency represses MRS3 mRNA translation through increased expression of antisense long non-coding RNA. Together, our results reveal complex gene expression and protein synthesis remodeling in response to low iron, demonstrating how this important metal affects protein translation at multiple levels.
