FMR1

Cilia effects upon perturbation of FMR1

Cilia number / % ciliated:

Decreased cilia number

Loss-of-function effect:

Shorter cilia

Ciliogenesis screen results (4 screens)

• Kim2016: No effect
• Wheway et al. 2015 (siRNA) [siRNA]: No effect PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680
• Roosing et al. 2015 (siRNA) [siRNA]: Joubert Candidate / Ciliogenesis Defect (robust z=-2.45, ciliated=18.8%) PMID:26595381

Phenotypes

Human ciliopathy phenotype:

fragile X-associated tremor/ataxia syndrome; Intellectual disability

Subcellular localization

cilia, nucleus

References: PMID:34848703, PMID:32735823, PMID:35438410

Functional category

• Ciliary assembly/disassembly
• Actin & cytoskeleton regulation
• Neurogenesis & migration
• Viral interactions
• Signaling (Hedgehog, GPCRs, ion channels)

Function

FMRP regulates transport efficacy, by regulating the association between mRNA cargo and and suggest a new mechanism for the Fragile X syndrome(18655836). Ciliary mRNP granules contained Fmrp, an RNA-binding protein (RBP) critical for neuronal plasticity by regulating local translation in neurites(25549890). Depriving the ciliary pool of Fmrp resulted in degeneration of ependymal multicilia(34848703). The number of primary cilia in Fmr1 KO mice is reduced, specifically in the DG of the hippocampus (32735823) FMRP loss leads to primary ciliary deficits in cerebellar Bergmann glia which may contribute to cerebellar deficits in FXS. (35438410) The mRNA-binding protein Fmrp localizes in the ciliary central lumen and appears to deliver mRNA into cilia, supporting local protein synthesis (Hao et al., 2021, Nat Commun, PMID 34848703).