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Abstract
The perinucleolar compartment (PNC) is a subnuclear stucture forming predominantly in cancer cells; its prevalence positively correlates with metastatic capacity. Although several RNA-binding proteins have been characterized in PNC, the molecular function of this compartment remains unclear. Here we demonstrate that the cyclin–dependent kinase 13 (CDK13) is a newly identified constituent of PNC. CDK13 is a kinase involved in the regulation of gene expression and whose overexpression was found to alter pre-mRNA processing. In this study we show that CDK13 is enriched in PNC and co-localizes all along the cell cycle with the PNC component PTB. In contrast, neither the cyclins K and L, known to associate with CDK13, nor the potential kinase substrates accumulate in PNC. We further show that CDK13 overexpression increases PNC prevalence suggesting that CDK13 may be determinant for PNC formation. This result linked to the finding that CDK13 gene is amplified in different types of cancer indicate that this kinase can contribute to cancer development in human.
Highlights
The cyclin–dependent kinases (CDKs) are a set of 20 ATP-dependent serine-threonine protein kinases acting in the integration of extracellular and intracellular signals to regulate cell-cycle progression and gene expression
The cyclin–dependent kinase 13 (CDK13) positive dots observed in interphase at the vicinity of the nucleolus do not co-localized with the splicing factor SRSF2, a marker of the speckles (Fig 1I–1K)
We demonstrate that CDK13 exhibits a noteworthy accumulation in perinucleolar compartment (PNC)
Summary
The cyclin–dependent kinases (CDKs) are a set of 20 ATP-dependent serine-threonine protein kinases acting in the integration of extracellular and intracellular signals to regulate cell-cycle progression and gene expression (for reviews see [1,2]). As transcription-related CDKs, CDK7, 8 and 9 act to regulate transcription initiation and elongation. Each of these kinases is part of a multisubunit complex, TFIIH, Mediator and pTEFB respectively. CDK12 and 13 evolved by duplication of a common gene ancestor, a single paralog being found in non-vertebrates deuterostomes [7,8]. In mammalian cells, both kinases operate in separate complexes, which could have different functions [9]. While both kinases were shown to participate in maintaining self-renewal ability in murine embryonic stem cells [10] or to PLOS ONE | DOI:10.1371/journal.pone.0149184 February 17, 2016
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