Protein Syndesmos is a novel RNA-binding protein that regulates primary cilia formation

• Published in: Nucleic acids research Vol. 46; no. 22; pp. 12067 - 12086
• Main Authors: Avolio, Rosario, Järvelin, Aino I, Mohammed, Shabaz, Agliarulo, Ilenia, Condelli, Valentina, Zoppoli, Pietro, Calice, Giovanni, Sarnataro, Daniela, Bechara, Elias, Tartaglia, Gian G, Landriscina, Matteo, Castello, Alfredo, Esposito, Franca, Matassa, Danilo S
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 14.12.2018
• Subjects: Cilia - genetics; Cilia - metabolism; Ciliopathies - genetics; HCT116 Cells; HeLa Cells; HSP90 Heat-Shock Proteins - metabolism; Humans; Neoplasms - genetics; Polyribosomes - metabolism; Protein Binding - genetics; Protein Biosynthesis - genetics; Protein Interaction Domains and Motifs - genetics; Protein Structure, Tertiary; RNA and RNA-protein complexes; RNA-Binding Proteins - chemistry; RNA-Binding Proteins - genetics; RNA-Binding Proteins - physiology
• ISSN: 0305-1048; 1362-4962
• DOI: 10.1093/nar/gky873

Abstract Syndesmos (SDOS) is a functionally poorly characterized protein that directly interacts with p53 binding protein 1 (53BP1) and regulates its recruitment to chromatin. We show here that SDOS interacts with another important cancer-linked protein, the chaperone TRAP1, associates with actively translating polyribosomes and represses translation. Moreover, we demonstrate that SDOS directly binds RNA in living cells. Combining individual gene expression profiling, nucleotide crosslinking and immunoprecipitation (iCLIP), and ribosome profiling, we discover several crucial pathways regulated post-transcriptionally by SDOS. Among them, we identify a small subset of mRNAs responsible for the biogenesis of primary cilium that have been linked to developmental and degenerative diseases, known as ciliopathies, and cancer. We discover that SDOS binds and regulates the translation of several of these mRNAs, controlling cilia development.