Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10801840 | Biochimica et Biophysica Acta (BBA) - Molecular Cell Research | 2016 | 12 Pages |
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.
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Authors
Ji Hyun Kim, Soo Mi Ki, Je-Gun Joung, Eric Scott, Susanne Heynen-Genel, Pedro Aza-Blanc, Chang Hyuk Kwon, Joon Kim, Joseph G. Gleeson, Ji Eun Lee,