The transcriptomic response of mixed neuron-glial cell cultures to 1,25-dihydroxyvitamin d3 includes genes limiting the progression of neurodegenerative diseases.

International audienceSeasonal or chronic vitamin D deficiency and/or insufficiency is highly prevalent in the human population. Receptors for 1,25-dihydroxyvitamin D3, the hormonal metabolite of vitamin D, are found throughout the brain. To provide further information on the role of this hormone on brain function, we analyzed the transcriptomic profiles of mixed neuron-glial cell cultures in response to 1,25-dihydroxyvitamin D3. 1,25-dihydroxyvitamin D3 treatment increases the mRNA levels of 27 genes by at least 1.9 fold. Among them, 17 genes were related to neurodegenerative and psychiatric diseases, or brain morphogenesis. Notably, 10 of these genes encode proteins potentially limiting the progression of Alzheimer's disease. These data provide support for a role of 1,25-dihydroxyvitamin D3 in brain disease prevention. The possible consequences of circannual or chronic vitamin D insufficiencies on a tissue with a low regenerative potential such as the brain should be considered

Norovirus infection results in eIF2α independent host translation shut-off and remodels the G3BP1 interactome evading stress granule formation.

Viral infections impose major stress on the host cell. In response, stress pathways can rapidly deploy defence mechanisms by shutting off the protein synthesis machinery and triggering the accumulation of mRNAs into stress granules to limit the use of energy and nutrients. Because this threatens viral gene expression, viruses need to evade these pathways to propagate. Human norovirus is responsible for gastroenteritis outbreaks worldwide. Here we examined how norovirus interacts with the eIF2α signaling axis controlling translation and stress granules. While norovirus infection represses host cell translation, our mechanistic analyses revealed that eIF2α signaling mediated by the stress kinase GCN2 is uncoupled from translational stalling. Moreover, infection results in a redistribution of the RNA-binding protein G3BP1 to replication complexes and remodelling of its interacting partners, allowing the avoidance from canonical stress granules. These results define novel strategies by which norovirus undergo efficient replication whilst avoiding the host stress response and manipulating the G3BP1 interactome

Rabies virus matrix protein interplay with eIF3, new insights into rabies virus pathogenesis

Viral proteins are frequently multifunctional to accommodate the high density of information encoded in viral genomes. Matrix (M) protein of negative-stranded RNA viruses such as Rhabdoviridae is one such example. Its primary function is virus assembly/budding but it is also involved in the switch from viral transcription to replication and the concomitant down regulation of host gene expression. In this study we undertook a search for potential rabies virus (RV) M protein's cellular partners. In a yeast two-hybrid screen the eIF3h subunit was identified as an M-interacting cellular factor, and the interaction was validated by co-immunoprecipitation and surface plasmon resonance assays. Upon expression in mammalian cell cultures, RV M protein was localized in early small ribosomal subunit fractions. Further, M protein added in trans inhibited in vitro translation on mRNA encompassing classical (Kozak-like) 5′-UTRs. Interestingly, translation of hepatitis C virus IRES-containing mRNA, which recruits eIF3 via a different noncanonical mechanism, was unaffected. Together, the data suggest that, as a complement to its functions in virus assembly/budding and regulation of viral transcription, RV M protein plays a role in inhibiting translation in virus-infected cells through a protein–protein interaction with the cellular translation machinery

Pumilio directs deadenylation-associated translational repression of the cyclin-dependent kinase 1 activator RGC-32

Response gene to complement-32 (RGC-32) activates cyclin-dependent kinase 1, regulates the cell cycle and is deregulated in many human tumours. We previously showed that RGC-32 expression is upregulated by the cancer-associated Epstein-Barr virus (EBV) in latently infected B cells through the relief of translational repression. We now show that EBV infection of naïve primary B cells also induces RGC-32 protein translation. In EBV-immortalised cell lines, we found that RGC-32 depletion resulted in cell death, indicating a key role in B cell survival. Studying RGC-32 translational control in EBV-infected cells, we found that the RGC-32 3′untranslated region (3′UTR) mediates translational repression. Repression was dependent on a single Pumilio binding element (PBE) adjacent to the polyadenylation signal. Mutation of this PBE did not affect mRNA cleavage, but resulted in increased polyA tail length. Consistent with Pumilio-dependent recruitment of deadenylases, we found that depletion of Pumilio in EBV-infected cells increased RGC-32 protein expression and polyA tail length. The extent of Pumilio binding to the endogenous RGC-32 mRNA in EBV-infected cell lines also correlated with RGC-32 protein expression. Our data demonstrate the importance of RGC-32 for the survival of EBV-immortalised B cells and identify Pumilio as a key regulator of RGC-32 translation

Léonce Bouyssou, Retables de Haute Auvergne — XVIIe- XIXe siècles, Collection « l'Encyclopédie du Massif central », Nonette, Editions CREER, 1991, 352 p.

Brocard-Plaut Michèle. Léonce Bouyssou, Retables de Haute Auvergne — XVIIe- XIXe siècles, Collection « l'Encyclopédie du Massif central », Nonette, Editions CREER, 1991, 352 p.. In: Bulletin Monumental, tome 151, n°2, année 1993. pp. 448-450

S. De Montessus De Ballore Lecointre, Retables et tabernacles des XVIIe et XVIIIe siècles dans les églises de la Creuse.

Brocard-Plaut Michèle. S. De Montessus De Ballore Lecointre, Retables et tabernacles des XVIIe et XVIIIe siècles dans les églises de la Creuse.. In: Bulletin Monumental, tome 148, n°2, année 1990. pp. 221-222

S. De Montessus De Ballore Lecointre, Retables et tabernacles des XVIIe et XVIIIe siècles dans les églises de la Creuse.

Brocard-Plaut Michèle. S. De Montessus De Ballore Lecointre, Retables et tabernacles des XVIIe et XVIIIe siècles dans les églises de la Creuse.. In: Bulletin Monumental, tome 148, n°2, année 1990. pp. 221-222

Léonce Bouyssou, Retables de Haute Auvergne — XVIIe- XIXe siècles, Collection « l'Encyclopédie du Massif central », Nonette, Editions CREER, 1991, 352 p.

Brocard-Plaut Michèle. Léonce Bouyssou, Retables de Haute Auvergne — XVIIe- XIXe siècles, Collection « l'Encyclopédie du Massif central », Nonette, Editions CREER, 1991, 352 p.. In: Bulletin Monumental, tome 151, n°2, année 1993. pp. 448-450

Christiane Lorgues-Lapouge, Trésor des vallées niçoises. Les peintures murales du haut pays., Nice, Editions Serres et Chambre de commerce de Nice et des Alpes-Maritimes, 1990, 142 p.

Brocard-Plaut Michèle. Christiane Lorgues-Lapouge, Trésor des vallées niçoises. Les peintures murales du haut pays., Nice, Editions Serres et Chambre de commerce de Nice et des Alpes-Maritimes, 1990, 142 p.. In: Bulletin Monumental, tome 149, n°2, année 1991. pp. 256-257

Christiane Lorgues-Lapouge, Trésor des vallées niçoises. Les peintures murales du haut pays., Nice, Editions Serres et Chambre de commerce de Nice et des Alpes-Maritimes, 1990, 142 p.

Brocard-Plaut Michèle. Christiane Lorgues-Lapouge, Trésor des vallées niçoises. Les peintures murales du haut pays., Nice, Editions Serres et Chambre de commerce de Nice et des Alpes-Maritimes, 1990, 142 p.. In: Bulletin Monumental, tome 149, n°2, année 1991. pp. 256-257