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Vol. 20, Issue 8, 2242-2253, April 15, 2009

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Core Exosome-independent Roles for Rrp6 in Cell Cycle Progression

Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, OH 44106

Submitted August 12, 2008; Revised February 3, 2009; Accepted February 11, 2009
Monitoring Editor: A. Gregory Matera

Exosome complexes are 3' to 5' exoribonucleases composed of subunits that are critical for numerous distinct RNA metabolic (ribonucleometabolic) pathways. Several studies have implicated the exosome subunits Rrp6 and Dis3 in chromosome segregation and cell division but the functional relevance of these findings remains unclear. Here, we report that, in Drosophila melanogaster S2 tissue culture cells, dRrp6 is required for cell proliferation and error-free mitosis, but the core exosome subunit Rrp40 is not. Micorarray analysis of dRrp6-depleted cell reveals increased levels of cell cycle– and mitosis-related transcripts. Depletion of dRrp6 elicits a decrease in the frequency of mitotic cells and in the mitotic marker phospho-histone H3 (pH3), with a concomitant increase in defects in chromosome congression, separation, and segregation. Endogenous dRrp6 dynamically redistributes during mitosis, accumulating predominantly but not exclusively on the condensed chromosomes. In contrast, core subunits localize predominantly to MTs throughout cell division. Finally, dRrp6-depleted cells treated with microtubule poisons exhibit normal kinetochore recruitment of the spindle assembly checkpoint protein BubR1 without restoring pH3 levels, suggesting that these cells undergo premature chromosome condensation. Collectively, these data support the idea that dRrp6 has a core exosome-independent role in cell cycle and mitotic progression.

Address correspondence to: Erik Andrulis (erik.andrulis{at}case.edu)

Abbreviations used: MT, microtubule; pH3, phospho-histone H3; PCL, perichromosomal layer; PCM, pericentriolar material; RNAi, RNA interference; SAC, spindle assembly checkpoint.

This article has been cited by other articles:

				M. Mamolen, A. Smith, and E. D. Andrulis Drosophila melanogaster Dis3 N-terminal domains are required for ribonuclease activities, nuclear localization and exosome interactions Nucleic Acids Res., April 26, 2010; (2010) gkq295v1. [Abstract] [Full Text] [PDF]

				D. L. Kiss and E. D. Andrulis Genome-wide analysis reveals distinct substrate specificities of Rrp6, Dis3, and core exosome subunits RNA, April 1, 2010; 16(4): 781 - 791. [Abstract] [Full Text] [PDF]