title: Global Analysis of mRNA, Translation, and Protein Localization: Local Translation Is a Key Regulator of Cell Protrusions.
abstract: Polarization of cells into a protrusive front and a retracting cell body is the hallmark of mesenchymal-like cell migration. Many mRNAs are localized to protrusions, but it is unclear to what degree mRNA localization contributes toward protrusion formation. We performed global quantitative analysis of the distributions of mRNAs, proteins, and translation rates between protrusions and the cell body by RNA sequencing (RNA-seq) and quantitative proteomics. Our results reveal local translation as a key determinant of protein localization to protrusions. Accordingly, inhibition of local translation destabilizes protrusions and inhibits mesenchymal-like morphology. Interestingly, many mRNAs localized to protrusions are translationally repressed. Specific cis-regulatory elements within mRNA UTRs define whether mRNAs are locally translated or repressed. Finally, RNAi screening of RNA-binding proteins (RBPs) enriched in protrusions revealed trans-regulators of localized translation that are functionally important for protrusions. We propose that by deciphering the localized mRNA UTR code, these proteins regulate protrusion stability and mesenchymal-like morphology.
authors.affiliation: Division of Cancer Biology, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK. Electronic address: mardakheh@icr.ac.uk.
authors.forename: Faraz K
authors.initials: FK
authors.lastname: Mardakheh
authors.affiliation: Division of Cancer Biology, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK.
authors.forename: Angela
authors.initials: A
authors.lastname: Paul
authors.affiliation: Division of Cancer Biology, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK.
authors.forename: Sandra
authors.initials: S
authors.lastname: Kümper
authors.affiliation: Division of Cancer Biology, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK.
authors.forename: Amine
authors.initials: A
authors.lastname: Sadok
authors.affiliation: Division of Cancer Biology, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK.
authors.forename: Hugh
authors.initials: H
authors.lastname: Paterson
authors.affiliation: Division of Cancer Biology, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK.
authors.forename: Afshan
authors.initials: A
authors.lastname: Mccarthy
authors.affiliation: Division of Molecular Pathology, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK.
authors.forename: Yinyin
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Division of Cancer Biology, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Marshall
mesh_terms: D002465:Cell Movement / Q000235:genetics*; D022081:Cell Surface Extensions / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics*; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics; D017423:Sequence Analysis, RNA / Q000379:methods
chemical_list: D012333:RNA, Messenger; D016601:RNA-Binding Proteins