Protein Syndesmos is a novel RNA-binding protein that regulates primary cilia formation.
Protein Syndesmos is a novel RNA-binding protein that regulates primary cilia formation.
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DOI：
10.1093/nar/gky873
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发表时间：
2018-12-14
影响因子：
14.9
通讯作者：
Matassa DS
中科院分区：
文献类型：
--
作者：
Avolio R;Järvelin AI;Mohammed S;Agliarulo I;Condelli V;Zoppoli P;Calice G;Sarnataro D;Bechara E;Tartaglia GG;Landriscina M;Castello A;Esposito F;Matassa DS
Syndesmos（SDOS）是一种功能不佳的蛋白质，其直接与p53结合蛋白1（53BP1）相互作用并调节其向染色质的募集。我们在这里表明，SDOS与另一个重要的癌症相关蛋白，伴侣TRAP1，与积极翻译多聚核糖体和抑制翻译。此外，我们证明了SDOS直接结合活细胞中的RNA。结合单个基因表达谱，核苷酸交联和免疫沉淀（iCLIP），核糖体分析，我们发现了几个关键的途径调节转录后SDOS。其中，我们确定了一个小的mRNA的子集，负责初级纤毛的生物发生，已被链接到发育和退行性疾病，称为ciliopathies，和癌症。我们发现SDOS结合并调节这些mRNA的翻译，控制纤毛发育。
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.