Cilia locally synthesize proteins to sustain their ultrastructure and functions

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 ultrastructure and functions. Multicilia of mouse ependymal cells were abundant in ribosomal proteins, translation initiation factors, and RNA, including 18S rRNA and tubulin mRNA. The cilia actively generated nascent peptides, including those of tubulin. FMRP, an RNA-binding component of messenger ribonucleoprotein granules critical for local translation, was concentrated in ciliary central lumen. Its depletion by RNAi impaired ciliary nascent peptide production and induced multicilia degeneration. Expression of exogenous FMRP, but not an isoform tethered to mitochondria, rescued the degeneration defects. Therefore, local translation defects in cilia might contribute to the pathology of ciliopathies and other diseases such as Fragile X syndrome. Purified ciliary mRNA profiles of ctrl-i and Fmr-i1 by deep sequencing with two biological replicates.