Abstract

SummaryWe previously reported that the small nuclear RNA processing complex, Integrator, is required for dynein recruitment to the nuclear envelope at mitotic onset in cultured human cells. We now report an additional role for INT in ciliogenesis. Depletion of INT subunits from cultured human cells results in loss of primary cilia. We provide evidence that the requirements for INT in dynein localization and ciliogenesis are uncoupled: proteins essential for ciliogenesis are not essential for dynein recruitment to the nuclear envelope, while depletion of known regulators of perinuclear dynein has minimal effects on ciliogenesis. Taken together, our data support a model in which INT ensures proper processing of distinct pools of transcripts encoding components that independently promote perinuclear dynein enrichment and ciliogenesis.

Highlights

  • Cytoplasmic dynein is a large, multimeric, minus-end-directed motor complex that associates with the dynein-activating complex, dynactin. (Holzbaur and Vallee, 1994; Kardon and Vale, 2009; Schroer, 2004)

  • Summary We previously reported that the small nuclear RNA processing complex, Integrator, is required for dynein recruitment to the nuclear envelope at mitotic onset in cultured human cells

  • We provide evidence that the requirements for INT in dynein localization and ciliogenesis are uncoupled: proteins essential for ciliogenesis are not essential for dynein recruitment to the nuclear envelope, while depletion of known regulators of perinuclear dynein has minimal effects on ciliogenesis

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Summary

Introduction

Cytoplasmic dynein is a large, multimeric, minus-end-directed motor complex that associates with the dynein-activating complex, dynactin. (Holzbaur and Vallee, 1994; Kardon and Vale, 2009; Schroer, 2004). During G2/M of cell division in multiple species, a pool of dynein anchored to the nuclear envelope (NE) facilitates nucleuscentrosome coupling, an essential step for proper mitotic spindle formation (Anderson et al, 2009; Bolhy et al, 2011; Gonczy et al, 1999; Jodoin et al, 2012; Malone et al, 2003; Robinson et al, 1999; Sitaram et al, 2012; Splinter et al, 2010; Vaisberg et al, 1993). The first two components, Bicaudal D2 (BICD2) and Centromere protein F (CENP-F), independently bind dynein subunits/adaptor proteins and nucleoporins to stably tether dynein complexes to the NE (Bolhy et al, 2011; Splinter et al, 2010). The third recently identified component, the small nuclear RNA (snRNA) complex, Integrator (INT), likely regulates dynein recruitment to the NE in an indirect manner distinct from that of BICD2 and CENP-F (Jodoin et al, 2013)

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