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At the crossway of ER-stress and proinflammatory responses

Reverendo, Marisa; Mendes, Andreia; Argüello, Rafael J.; Gatti, Evelina; Pierre, Philippe

Immune cells detect specific microbes or damage to tissue integrity in order to initiate efficient immune responses. Abnormal accumulation of proteins in the endoplasmic reticulum (ER) can be seen as a sign of cellular malfunction and stress that triggers a collection of conserved emergency rescue programs. These different signaling cascades, which favor ER proteostasis and promote cell survival, are collective...


Polymerase III transcription is necessary for T cell priming by dendritic cells

Reverendo, Marisa; Argüello, Rafael J.; Polte, Christine; Valecka, Jan; Camosseto, Voahirana; Auphan-Anezin, Nathalie; Ignatova, Zoya; Gatti, Evelina

Exposure to microbe-associated molecular patterns (MAMPs) causes dendritic cells (DCs) to undergo a remarkable activation process characterized by changes in key biochemical mechanisms. These enhance antigen processing and presentation, as well as strengthen DC capacity to stimulate naïve T cell proliferation. Here, we show that in response to the MAMPS lipopolysaccharide and polyriboinosinic:polyribocytidylic ...


Protein synthesis inhibition and GADD34 control IFN-β heterogeneous expression ...

Dalet, Alexandre; Argüello, Rafael J.; Combes, Alexis; Spinelli, Lionel; Jaeger, Sebastien; Fallet, Mathieu; Manh, Thien-Phong Vu; Mendes, Andreia

In innate immune responses, induction of type-I interferons (IFNs) prevents virus spreading while viral replication is delayed by protein synthesis inhibition. We asked how cells perform these apparently contradictory activities. Using single fibroblast monitoring by flow cytometry and mathematical modeling, we demonstrate that type-I IFN production is linked to cell's ability to enter dsRNA-activated PKR-depen...


Conserved and highly expressed tRNA derived fragments in zebrafish

Soares, Ana Raquel; Fernandes, Noémia; Reverendo, Marisa; Araújo, Hugo Rafael; Oliveira, José Luís; Moura, Gabriela M. R.; Santos, Manuel A. S.

Background: Small non-coding RNAs (sncRNAs) are a class of transcripts implicated in several eukaryotic regulatory mechanisms, namely gene silencing and chromatin regulation. Despite significant progress in their identification by next generation sequencing (NGS) we are still far from understanding their full diversity and functional repertoire. Results: Here we report the identification of tRNA derived fragmen...


Differences in the expression pattern of HCN isoforms among mammalian tissues: ...

Calejo, Ana I.; Reverendo, Marisa; Silva, Virgília S.; Pereira, Patrícia M.; Santos, Manuel A. S.; Zorec, Robert; Gonçalves, Paula P.

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play a critical role in a broad range of cell types, but the expression of the various HCN isoforms is still poorly understood. In the present study we have compared the expression of HCN isoforms in rat excitable and non-excitable tissues at both the mRNA and protein levels. Real-time PCR and Western blot analysis revealed distinct expression p...


TRNA mutations that affect decoding fidelity deregulate development and the pro...

Reverendo, Marisa; Soares, Ana R.; Pereira, Patrícia M.; Carreto, Laura; Ferreira, Violeta; Gatti, Evelina; Pierre, Philippe; Moura, Gabriela R.

Mutations in genes that encode tRNAs, aminoacyl-tRNA syntheases, tRNA modifying enzymes and other tRNA interacting partners are associated with neuropathies, cancer, type-II diabetes and hearing loss, but how these mutations cause disease is unclear. We have hypothesized that levels of tRNA decoding error (mistranslation) that do not fully impair embryonic development can accelerate cell degeneration through pr...


Dre-miR-2188 targets Nrp2a and mediates proper intersegmental vessel developmen...

Soares, Ana R.; Reverendo, Marisa; Pereira, Patrícia M.; Nivelles, Olivier; Pendeville, Hélène; Bezerra, Ana Rita; Moura, Gabriela R.; Struman, Ingrid

Background - MicroRNAs (miRNAs) are a class of small RNAs that are implicated in the control of eukaryotic gene expression by binding to the 3′UTR of target mRNAs. Several algorithms have been developed for miRNA target prediction however, experimental validation is still essential for the correct identification of miRNA targets. We have recently predicted that Neuropilin2a (Nrp2a), a vascular endothelial growt...


Ethanol exposure induces upregulation of specific microRNAs in zebrafish embryos

Soares, Ana Raquel; Pereira, Patrícia M.; Ferreira, Violeta; Reverendo, Marisa; Simões, João; Bezerra, Ana Rita; Moura, Gabriela R.

Prenatal exposure to ethanol leads to a myriad of developmental disorders known as fetal alcohol spectrum disorder, often characterized by growth and mental retardation, central nervous system damage, and specific craniofacial dysmorphic features. The mechanisms of ethanol toxicity are not fully understood, but exposure during development affects the expression of several genes involved in cell cycle control, a...


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