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Cremaschi, J.

Publications and source records attributed to Cremaschi, J..

3 recordsLinked to original sources

Dicer accumulates in cytoplasmic foci upon alphavirus infection and plays a proviral role in Myotis myotis bat cells

Bats are reservoirs for many viruses that frequently cause epidemics in humans and animals. It is thus critical to better understand their immune system and mechanisms of antiviral immunity. Despite an increasing number of studies, much is still unknown about the molecular mechanisms that govern bat-virus interactions, especially given the large diversity of bat species. Dicer is a conserved ribonuclease with multiple activities that can modulate antiviral immunity, including the detection of viral RNA as part of the RNA interference (RNAi) pathway, the maturation of micro RNAs, and the direct inhibition of innate immunity in mouse and human cells. In view of these complex activities of Dicer, we tested its antiviral activity in Myotis myotis nasal epithelial cells. Surprisingly, we did not see strong evidence of RNAi in these cells, but instead saw a proviral effect of Dicer for two alphaviruses, Sindbis and Semliki forest virus. We also observed a striking relocalization of Dicer to cytoplasmic foci upon infection with these viruses, which did not occur in the several human cell lines we tested. These foci contained dsRNA and viral plus strand RNA, suggesting that they are sites of viral replication. Finally, we found that factors specific to M. myotis cells are needed for Dicer relocalization. Overall, we propose that Dicer can play different roles in different bat species and/or cell types, and is being repurposed by alphaviruses to promote viral replication.

microbiology↗

piRNAs are regulators of metabolic reprogramming in stem cells

Stem cells preferentially use glycolysis instead of oxidative phosphorylation and this metabolic rewiring plays an instructive role in their fate; however, the underlying molecular mechanisms remain largely unexplored. PIWI-interacting RNAs (piRNAs) and PIWI proteins have essential functions in a range of adult stem cells across species. Here, we show that piRNAs and the PIWI protein Aubergine (Aub) are instrumental in activating glycolysis in Drosophila germline stem cells (GSCs). High glycolysis is required for GSC self-renewal and aub loss-of-function induces a metabolic switch in GSCs leading to their differentiation. Aub directly binds glycolytic mRNAs and Enolase mRNA regulation by Aub depends on its 5UTR. Furthermore, deletion of a piRNA target site in Enolase 5UTR leads to GSC loss. These data reveal an Aub/piRNA function in translational activation of glycolytic mRNAs in GSCs, and pinpoint a new mode of regulation of metabolic reprogramming in stem cells based on small RNAs.

developmental biology↗

The PIWI protein Aubergine recruits eIF3 to activate translation in the germ plasm

Piwi-interacting RNAs (piRNAs) and PIWI proteins are essential in germ cells to repress transposons and regulate mRNAs. In Drosophila, piRNAs bound to the PIWI protein Aubergine (Aub) are transferred maternally to the embryo and regulate maternal mRNA stability through two opposite roles. They target mRNAs by incomplete base-pairing, leading to both their destabilization in the soma, and stabilization in the germ plasm. Here, we report a function of Aub in translation. Aub is required for translational activation of nanos mRNA, a key determinant of the germ plasm. Aub physically interacts with the poly(A) binding protein PABP and the translation initiation factor eIF3. Polysome gradient profiling identifies Aub role at the initiation step of translation. In the germ plasm, PABP and eIF3d assemble in foci that surround Aub-containing germ granules, and Aub acts with eIF3d to promote nanos translation. These results reveal a new mode of mRNA regulation by Aub, highlighting PIWI protein versatility in mRNA regulation.

developmental biology↗