title: Genome-wide screen identifies novel machineries required for both ciliogenesis and cell cycle arrest upon serum starvation.
abstract: Biogenesis of the primary cilium, a cellular organelle mediating various signaling pathways, is generally coordinated with cell cycle exit/re-entry. Although the dynamic cell cycle-associated profile of the primary cilium has been largely accepted, the mechanism governing the link between ciliogenesis and cell cycle progression has been poorly understood. Using a human genome-wide RNAi screen, we identify genes encoding subunits of the spliceosome and proteasome as novel regulators of ciliogenesis. We demonstrate that 1) the mRNA processing-related hits are essential for RNA expression of molecules acting in cilia disassembly, such as AURKA and PLK1, and 2) the ubiquitin-proteasome systems (UPS)-involved hits are necessary for proteolysis of molecules acting in cilia assembly, such as IFT88 and CPAP. In particular, we show that these screen hit-associated mechanisms are crucial for both cilia assembly and cell cycle arrest in response to serum withdrawal. Finally, our data suggest that the mRNA processing mechanism may modulate the UPS-dependent decay of cilia assembly regulators to control ciliary resorption-coupled cell cycle re-entry.
authors.affiliation: Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, #81 Irwon-Ro Gangnam-Gu, Seoul 06351, Republic of Korea.
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, #81 Irwon-Ro Gangnam-Gu, Seoul 06351, Republic of Korea.
authors.forename: Soo Mi
authors.initials: SM
authors.lastname: Ki
authors.affiliation: SGI, Samsung Medical Center, #81 Irwon-Ro Gangnam-Gu, Seoul 06351, Republic of Korea.
authors.forename: Je-Gun
authors.initials: JG
authors.lastname: Joung
authors.affiliation: Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Scott
authors.affiliation: High Content Screening and Functional Genomics Core, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA.
authors.forename: Susanne
authors.initials: S
authors.lastname: Heynen-Genel
authors.affiliation: High Content Screening and Functional Genomics Core, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA.
authors.forename: Pedro
authors.initials: P
authors.lastname: Aza-Blanc
authors.affiliation: SGI, Samsung Medical Center, #81 Irwon-Ro Gangnam-Gu, Seoul 06351, Republic of Korea.
authors.forename: Chang Hyuk
authors.initials: CH
authors.lastname: Kwon
authors.affiliation: GSMSE, KAIST, 291 Daehak-Ro, Yuseong-gu, Daejeon 34141, Republic of Korea.
authors.forename: Joon
authors.initials: J
authors.lastname: Kim
authors.affiliation: Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA. Electronic address: jogleeson@rockefeller.edu.
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Gleeson
authors.affiliation: Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, #81 Irwon-Ro Gangnam-Gu, Seoul 06351, Republic of Korea; SGI, Samsung Medical Center, #81 Irwon-Ro Gangnam-Gu, Seoul 06351, Republic of Korea. Electronic address: jieun.lee@skku.edu.
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Lee
mesh_terms: D015153:Blotting, Western; D002453:Cell Cycle / Q000235:genetics*; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics*; D002460:Cell Line; D002923:Cilia / Q000378:metabolism* / Q000502:physiology; D016000:Cluster Analysis; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D020869:Gene Expression Profiling / Q000379:methods; D053263:Gene Regulatory Networks / Q000235:genetics; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D008957:Models, Genetic; D009024:Morphogenesis / Q000235:genetics; D020543:Proteome / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome / Q000235:genetics*
chemical_list: D016895:Culture Media, Serum-Free; D008164:Luminescent Proteins; D020543:Proteome
keywords: Cell cycle; Ciliogenesis; High-content screen; Ubiquitin–proteasome system; mRNA processing