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Cailloce, J.

Publications and source records attributed to Cailloce, J..

2 recordsLinked to original sources

Multiple pathways prevent bi-parental mitochondria transmission in C. elegans

The uniparental transmission of the maternal mitochondrial genome is achieved by the disposal of the sperm mitochondria and their DNA (mtDNA) around fertilization. C. elegans embryo allowed the identification of several factors and mechanisms involved after fertilization. The discovery that the autophagy pathway and its adaptor ALLO-1 are implicated represented a major progress. In addition, studies in fish and fly have implicated CPS-6, a sperm mitochondrial endonuclease, in the degradation of C. elegans sperm-derived mtDNA. The sperm mitochondria-associated proteins FNDC-1 and PHB-2 were also implicated in efficiently removing sperm-derived mitochondria. Despite these recent findings, it is still not clear whether they account for the complete degradation and if we can experimentally prevent sperm-mitochondria clearance and induce sperm-mtDNA transmission to the progeny. Here, we investigated the genetic interactions and tested the impact of simultaneous inactivation of known factors on the fate of sperm-derived mitochondria and their mtDNA. We revealed an additive effect of ALLO-1 and CPS-6 loss of function. Furthermore, the inactivation of known factors acting in sperm mitochondria clearance was not sufficient to avoid sperm mitochondria removal and to allow paternal mtDNA inheritance across generations. These findings reveal that C. elegans employs at least two parallel pathways to ensure the degradation of paternal mitochondria and suggest the presence of unidentified mechanism(s) safeguarding maternal mitochondrial inheritance.

developmental biology↗

Aurora-A phosphorylates splicing factors and regulates alternative splicing

Aurora-A kinase is well known to regulate progression through mitosis. However, the kinase also performs additional functions that could explain the failure of its inhibitors to be effective in cancer treatments. To identify these functions, we applied a proteomics approach to search for interactors of Aurora-A. We found a large number of proteins involved in pre-mRNA splicing, strongly suggesting an important role for Aurora-A in this biological process. Consistently, we first report the subcellular localization of Aurora-A in nuclear speckles, the storehouse of splicing proteins. We also demonstrate direct interaction of Aurora-A with RRM domain-containing splicing factors such as hnRNP and SR proteins and their phosphorylation in vitro. Further, RNA-sequencing analysis following pharmacological inhibition of Aurora-A resulted in alternative splicing changes corresponding to 505 genes, including genes with functions regulated by Aurora-A kinase. Finally, we report enrichment of RNA motifs within the alternatively spliced regions affected by Aurora-A kinase inhibition which are bound by Aurora-A interacting splicing factors, suggesting that Aurora-A regulates alternative splicing by modulating the activity of these interacting splicing factors. Overall our work identified Aurora-A as a novel splicing kinase and for the first time, describes a broad role of Aurora-A in regulating alternative splicing.

molecular biology↗