Crucial metabolic functions of peroxisomes rely on a variety of peroxisomal membrane proteins (PMPs). While mRNA transcripts of PMPs were shown to be colocalized with peroxisomes, the process by which PMPs efficiently couple translation with targeting to the peroxisomal membrane remained elusive. Here, we combine quantitative electron microscopy with proximity-specific ribosome profiling and reveal that translation of specific PMPs occurs on the surface of peroxisomes in the yeast Saccharomyces cerevisiae. This places peroxisomes alongside chloroplasts, mitochondria, and the endoplasmic reticulum as organelles that use localized translation for ensuring correct insertion of hydrophobic proteins into their membranes. Moreover, the correct targeting of these transcripts to peroxisomes is crucial for peroxisomal and cellular function, emphasizing the importance of localized translation for cellular physiology.
|State||Published - Jan 2022|
Bibliographical noteFunding Information:
We thank Y. Peleg for constructing pMS1006 and pMS1007 used in Fig. 1; R. Erdmann for sharing pMS894 CFP-PTS1 peroxisomal marker plasmid used in all smRNA-FISH experiments and for exciting discussions on Pex19; J. Gerst and R.-R. Nair for sharing the strains Pex11-MS2L and Pex14-MS2L, the tethering element plasmid used for Fig. 4, and the Cy3-tagged MS2L probe used for the smRNA-FISH performed in Fig. 4 and for their intellectual contributions to thinking about localized translation; and M. Carmi for assisting with establishing the smRNA-FISH methodology in our laboratory. We are indebted to O. Schuldiner and R. Dzikowski for critical reading of the manuscript and excellent suggestions during the writing process. The project performed in the M.S. laboratory was supported by the European Research Council Consolidator Grant Peroxisystem 646604 and then a European Research Council Consolidator Grant OnTarget 864068, an Israel Science Foundation grant (ISF 760/17), the Hadar Impact Fund, and the Edmond de Rothschild Foundations. Y.B. is supported by EMBO Long-term Postdoctoral Fellowships. M.S. in an incumbent of the Dr. Gilbert Omenn and Martha Darling Professorial Chair in Molecular Genetics. The robotic system of the M.S. laboratory was purchased through the support of the Blythe Brenden-Mann Foundation.
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