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Global Analysis of Translational Reprogramming during Flagellar Regeneration Reveals the Role of Sphingolipid Metabolism in Ciliogenesis and Ciliopathies

ABSTRACT: Protein synthesis is essential for cilium assembly, but little is known about translational reprogramming that occurs during ciliogenesis. Using ribosome footprinting, we perform global translatome profiling on Chlamydomonas during flagellar regeneration.

ORGANISM(S): Chlamydomonas reinhardtii Caenorhabditis elegans

PROVIDER: GSE149844 | GEO | 2022/04/28

REPOSITORIES: GEO

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Global Analysis of Translational Reprogramming during Flagellar Regeneration Reveals the Role of Sphingolipid Metabolism in Ciliogenesis and Ciliopathies

Project description:Global Analysis of Translational Reprogramming during Flagellar Regeneration Reveals the Role of Sphingolipid Metabolism in Ciliogenesis and Ciliopathies

| PRJNA630259 | ENA

Cilium induction triggers differentiation of glioma stem cells

Project description:Glioblastoma multiforme (GBM) possesses glioma stem cells (GSCs) that promote self-renewal, tumor propagation, and relapse. Understanding the mechanisms of GSCs self-renewal can offer targeted therapeutic interventions. However, insufficient knowledge of the fundamental biology of GSCs is a significant bottleneck hindering these efforts. Here, we show that patient-derived GSCs recruit an elevated level of proteins that ensure the temporal cilium disassembly, leading to suppressed ciliogenesis. Depleting the cilia disassembly complex components at the ciliary base is sufficient to induce ciliogenesis in a subset of GSCs via sequestering PDGFR-α from its original location to newly induced cilium. Importantly, restoring ciliogenesis caused GSCs to behave like healthy NPCs switching from self-renewal to differentiation. Finally, using an organoid-based glioma invasion assay and brain xenografts in mice, we establish that ciliogenesis-induced differentiation can prevent the infiltration of GSCs into the brain. Our findings illustrate a crucial role for cilium as a molecular switch in determining GSCs' fate and suggest that cilium induction is an attractive strategy to intervene in GSCs proliferation.

2021-07-08 | GSE179439 | GEO

A ciliopathy complex restrains centriolar length and builds distal appendages to initiate ciliogenesis.

Project description:Mitosis segregates into each daughter cell two centrioles, the older of which is uniquely capable of generating a cilium. How this older centriole, called the mother centriole, initiates ciliogenesis remains poorly understood. We have identified an evolutionarily conserved complex comprised of CEP90, OFD1, MNR and FOPNL. Human mutations in CEP90, MNR and OFD1 cause ciliopathies. Super-resolution microscopy revealed that this complex forms a ring at the distal centriole. Centrioles of cells lacking MNR or CEP90 failed to assemble distal appendages and cannot generate cilia. In addition to the centrioles, complex members localized to centriolar satellites, proteinaceous granules surrounding the centrioles. Disruption of satellites did not affect distal appendage assembly, indicating that the centriolar pool is required for ciliogenesis. Consistent with an essential role in ciliogenesis, mice lacking MNR or CEP90 did not assemble cilia, did not survive beyond embryonic day 9.5, and did not transduce Hedgehog signals. In addition to ciliogenesis, MNR, but not CEP90, restrained centriolar length. MNR recruited both OFD1, required for centriolar length control, and CEP90, which recruits CEP83 to root distal appendages. Thus, an evolutionarily conserved ciliopathy-associated complex functions at the distal centriole to control centriole length and assemble distal appendages.

2021-06-15 | PXD022372 | Pride

MG1655 Flagellar Regulators RNA-seq

Project description:MG1655 Flagellar Regulators RNA-seq

| PRJEB6897 | ENA

Chlamy genome wide transcription

Project description:Genome-wide Transcriptional Analysis of Flagellar Regeneration in Chlamydomonas reinhardtii Identifies Orthologs of Ciliary Disease Genes Keywords: other

2005-01-17 | GSE2153 | GEO

The polar flagellar transcriptional regulatory network in Vibrio campbellii deviates from known Vibrio species

Project description:Vibrio campbellii is a gram-negative bacterial pathogen that is both free-living and a pathogen of marine organisms and exhibits swimming motility via a single, polar flagellum. Swimming motility is a critical virulence factor in V. campbellii pathogenesis, and disruption of the flagellar motor significantly decreases host mortality. However, while V. campbelli encodes homologs of flagellar and chemotaxis genes conserved by other members of the Vibrionaceae, the regulatory network governing these genes have not been explored. We systematically deleted all 63 known flagellar and chemotaxis genes in V. campbellii and examined their effects on motility compared to their homologs in other Vibrios. We specifically focused on assessing the roles of the core flagellar regulators of the flagellar regulatory hierarchy established in other Vibrios: rpoN, flrA, flrC, and fliA. Although V. campbellii transcription of flagellar and chemotaxis genes is governed by a multi-tiered regulatory hierarchy similar to other Vibrios, we observed two critical differences: the σ54-dependent regulator FlrA is dispensable for motility, and Class II gene expression is independent of σ54 regulation. Our genetic and phenotypic dissection of the V. campbellii flagellar regulatory network highlights the differences that have evolved in flagellar regulation across the Vibrionaceae.

2021-07-26 | GSE167483 | GEO

Transcriptional organization and regulation of the Pseudomonas putida flagellar system

Project description:The entire set of flagellar structural components and flagellar-specific transcriptional regulators, as well as much of the core chemotaxis machinery, is encoded into a >70 kbp cluster in Pseudomonas putida KT2440 genome. We have performed RNA-seq of the wild-type strain in order to identify operon boundaries and promoters location in this cluster.

2021-05-05 | GSE173832 | GEO

Chlamy genome wide transcription

Project description:Genome-wide Transcriptional Analysis of Flagellar Regeneration in Chlamydomonas reinhardtii Identifies Orthologs of Ciliary Disease Genes

2010-06-10 | E-GEOD-2153 | biostudies-arrayexpress

MG1655 Flagellar Regulators RNA-seq

Project description:This experiment contains RNA-seq data for a motile derivative of MG1655 and isogenic strains with deletions of each flagellar regulator: flhD, flhC, and fliA. All strains were grown at 37 degrees C in LB. After RNA purification, ribosomal RNA was removed using RiboZero and a library was made of remaining total RNA.

2014-08-01 | E-MTAB-2802 | biostudies-arrayexpress

Transcriptional profiling of C. elegans DAF-19 uncovers a ciliary base-associated protein and a CDK/CCRK/LF2p-related kinase required for intraflagellar transport.

Project description:Cilia are ubiquitous cell surface projections that modulate various sensory- and motility based processes and are implicated in a growing number of multi-organ genetic disorders termed ciliopathies. As new components required for cilium biogenesis and function remain unidentified, we sought to further define and validate the transcriptional targets of the ciliogenic C. elegans RFX transcription factor DAF-19. To this end, transcriptional profiling of daf-19 mutants (which do not form cilia) and wild-type animals was performed using selectively staged embryos where ciliogenesis occurs in most ciliated sensory neurons (CSNs). Statistical comparisons between the two populations revealed 881 differentially regulated genes with 1.5-fold change or greater. A subset of these was confirmed by quantitative RT-PCR. Transgenic worms expressing transcriptional-GFP fusions revealed CSN-specific expression patterns for 9 of 12 candidate genes. We show that two uncharacterized candidate genes, which we term dyf-17 and dyf-18 because their corresponding mutants display dye-filling (Dyf) defects, are important for ciliogenesis. DYF-17 localizes at the base of cilia and interestingly, is specifically required for building the distal segment of sensory cilia. DYF-18 is an evolutionarily conserved CDK-7/CCRK-related serine-threonine kinase that is necessary for the proper function of intraflagellar transport (IFT), a process critical for cilium biogenesis. Together, our comparative microarray study identifies targets of the evolutionarily conserved RFX transcription factor, DAF-19, providing a rich dataset from which to uncover—in addition to DYF-17 and DYF-18—cellular components important for cilium formation and function. 4 daf-19,daf12; 4 daf-12; 4 WT

2011-07-25 | E-GEOD-25633 | biostudies-arrayexpress

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