Identification of a novel nucleolar protein complex required for mitotic chromosome segregation through centromeric accumulation of Aurora B

Abstract

<jats:title>Abstract</jats:title> <jats:p>The nucleolus is a membrane-less nuclear structure that disassembles when cells undergo mitosis. During mitosis, nucleolar factors are thus released from the nucleolus and dynamically change their subcellular localization; however, their functions remain largely uncharacterised. Here, we found that a nucleolar factor called nucleolar protein 11 (NOL11) forms a protein complex with two tryptophan-aspartic acid (WD) repeat proteins named WD-repeat protein 43 (WDR43) and Cirhin in mitotic cells. This complex, referred to here as the NWC (NOL11-WDR43-Cirhin) complex, exists in nucleoli during interphase and translocates to the periphery of mitotic chromosomes, i.e., perichromosomal regions. During mitotic progression, both the congression of chromosomes to the metaphase plate and sister chromatid cohesion are impaired in the absence of the NWC complex, as it is required for the centromeric enrichment of Aurora B and the associating phosphorylation of histone H3 at threonine 3. These results reveal the characteristics of a novel protein complex consisting of nucleolar proteins, which is required for regulating kinetochores and centromeres to ensure faithful chromosome segregation.</jats:p>

Increased numbers of nucleoli in a genome-wide RNAi screen reveal proteins that link the cell cycle to RNA polymerase I transcription

“…It is thus interesting to speculate that these proteins may be required for the reinitiation of RNAPI transcription upon mitotic exit that, if disrupted, would lead to failure in the reformation and coalescence of nascent nucleoli. Furthermore, a novel complex of ribosome biogenesis factors was recently implicated in the regulation of mitotic entry, chromatid cohesion, and spindle assembly through AURKB ( Fujimura et al , 2020 ), strengthening the support for a cross-talk between ribosome biogenesis factors, nucleolar proteins, and mitosis. Thus, while it is possible that our screen hits function in ribosome biogenesis outside of mitosis, as reported previously for KIF11 in translation ( Bartoli et al , 2011 ), the enrichment of mitotic factors among the hits strongly supports the conclusion that the role for these proteins in mitosis also includes the regulation of RNAPI transcription.…”

Proteome Analysis of Condensed Barley Mitotic Chromosomes

“…Interestingly, the correct function of kinetochore depends on the translocation of the NOL11, WDR43, and Cirhin complex from the nucleoli to the perichromosomal layer. This is required for the centromeric enrichment of Aurora B and the subsequent phosphorylation of histone H3 ( Fujimura et al, 2020 ) and underlines the key role of nucleolar proteins in the function of mitotic chromosomes.…”

WD40 repeat 43 mediates cell survival, proliferation, migration and invasion via vimentin in colorectal cancer

“…Similarly, it was found by Zhao et al [ 17 ] that the loss of WDR43 in zebrafish caused early developmental defects in various tissues. In addition, Fujimura et al [ 18 ] proved that the nucleolar protein 11 (NOL11) forms a protein complex called NWC with WDR43 and Cirhin, and participates in the process of chromosome mitosis by promoting the enrichment of Aurora B on the centromere. The present study also reported an effect of WDR43 on the migratory ability of CRC cells, an effect that appeared to be achieved through the regulation of VIM, which was manifested as a significant decrease in VIM expression following WDR43 knockdown.…”