mRNA spindle localization and mitotic translational regulation by CPEB1 and CPEB4
- Rosa Pascual1,6,
- Carolina Segura-Morales1,7,
- Manja Omerzu2,
- Nicolás Bellora3,
- Eulàlia Belloc1,
- Chiara Lara Castellazzi1,
- Oscar Reina1,
- Eduardo Eyras4,5,8,
- Madelon M. Maurice2,
- Alba Millanes-Romero1 and
- Raúl Méndez1,5
- 1Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, 08028 Barcelona, Spain
- 2Oncode Institute and Department of Cell Biology, Centre for Molecular Medicine, University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands
- 3Instituto Andino Patagónico de Tecnologías Biológicas y Geoambientales (IPATEC), Universidad Nacional del Comahue—CONICET, S.C. de Bariloche, 8400, Argentina
- 4Department of Experimental and Health Sciences, Universidad Pompeu Fabra, Barcelona 08002, Spain
- 5Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona 08010, Spain
- Corresponding authors: raul.mendez{at}irbbarcelona.org, alba.millanes{at}irbbarcelona.org
Abstract
Transition through cell cycle phases requires temporal and spatial regulation of gene expression to ensure accurate chromosome duplication and segregation. This regulation involves dynamic reprogramming of gene expression at multiple transcriptional and posttranscriptional levels. In transcriptionally silent oocytes, the CPEB-family of RNA-binding proteins coordinates temporal and spatial translation regulation of stored maternal mRNAs to drive meiotic progression. CPEB1 mediates mRNA localization to the meiotic spindle, which is required to ensure proper chromosome segregation. Temporal translational regulation also takes place in mitosis, where a large repertoire of transcripts is activated or repressed in specific cell cycle phases. However, whether control of localized translation at the spindle is required for mitosis is unclear, as mitotic and acentriolar-meiotic spindles are functionally and structurally different. Furthermore, the large differences in scale-ratio between cell volume and spindle size in oocytes compared to somatic mitotic cells may generate distinct requirements for gene expression compartmentalization in meiosis and mitosis. Here we show that mitotic spindles contain CPE-localized mRNAs and translating ribosomes. Moreover, CPEB1 and CPEB4 localize in the spindles and they may function sequentially in promoting mitotic stage transitions and correct chromosome segregation. Thus, CPEB1 and CPEB4 bind to specific spindle-associated transcripts controlling the expression and/or localization of their encoded factors that, respectively, drive metaphase and anaphase/cytokinesis.
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Article is online at http://www.rnajournal.org/cgi/doi/10.1261/rna.077552.120.
- Received August 12, 2020.
- Accepted December 2, 2020.
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