State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, 320 Yueyang Road, 200031, Shanghai, China.
University of Chinese Academy of Sciences, 100049, Beijing, China.
Nat Commun. 2021 Nov 30;12(1):6971. doi: 10.1038/s41467-021-27298-1.
Cilia are microtubule-based hair-like organelles propelling locomotion and extracellular liquid flow or sensing environmental stimuli. As cilia are diffusion barrier-gated subcellular compartments, their protein components are thought to come from the cell body through intraflagellar transport or diffusion. Here we show that cilia locally synthesize proteins to maintain their structure and functions. Multicilia of mouse ependymal cells are abundant in ribosomal proteins, translation initiation factors, and RNA, including 18 S rRNA and tubulin mRNA. The cilia actively generate nascent peptides, including those of tubulin. mRNA-binding protein Fmrp localizes in ciliary central lumen and appears to function in mRNA delivery into the cilia. Its depletion by RNAi impairs ciliary local translation and induces multicilia degeneration. Expression of exogenous Fmrp, but not an isoform tethered to mitochondria, rescues the degeneration defects. Therefore, local translation defects in cilia might contribute to the pathology of ciliopathies and other diseases such as Fragile X syndrome.
纤毛是一种基于微管的毛发状细胞器,能够推动运动和细胞外液体流动,或感知环境刺激。由于纤毛是扩散屏障门控的亚细胞隔室,其蛋白成分被认为是通过鞭毛内运输或扩散从细胞体进入的。在这里,我们展示了纤毛可以局部合成蛋白质来维持其结构和功能。小鼠室管膜细胞的多纤毛富含核糖体蛋白、翻译起始因子和 RNA,包括 18S rRNA 和微管蛋白 mRNA。纤毛可以主动生成新生肽,包括微管蛋白的肽段。mRNA 结合蛋白 Fmrp 定位于纤毛中央管腔中,似乎在将 mRNA 递送到纤毛中发挥作用。用 RNAi 使其耗竭会损害纤毛的局部翻译,并诱导多纤毛退化。外源性 Fmrp 的表达(而非与线粒体结合的同种型)可以挽救退化缺陷。因此,纤毛中的局部翻译缺陷可能导致纤毛病和脆性 X 综合征等其他疾病的病理学变化。