22 documents found, page 1 of 3
Evaluation of the genetic risk for COVID-19 outcomes in COPD and differences am...
Marçalo, Rui; Neto, Sonya; Pinheiro, Miguel; Rodrigues, Ana J.; Sousa, Nuno; Santos, Manuel A. S.; Simão, Paula; Valente, Carla; Andrade, LíliaPopulations seem to respond differently to the global pandemic of severe acute respiratory syndrome coronavirus 2. Recent studies show individual variability in both susceptibility and clinical response to COVID-19 infection. People with chronic obstructive pulmonary disease (COPD) constitute one of COVID-19 risk groups, being already associated with a poor prognosis upon infection. This study aims contributing...
Plasmodium apicoplast tyrosyl-tRNA synthetase recognizes an unusual, simplified...
Cela, Marta; Paulus, Caroline; Santos, Manuel A. S.; Moura, Gabriela R.; Frugier, Magali; Rudinger-Thirion, JoëlleThe life cycle of Plasmodium falciparum, the agent responsible for malaria, depends on both cytosolic and apicoplast translation fidelity. Apicoplast aminoacyl-tRNA synthetases (aaRS) are bacterial-like enzymes devoted to organellar tRNA aminoacylation. They are all encoded by the nuclear genome and are translocated into the apicoplast only after cytosolic biosynthesis. Apicoplast aaRSs contain numerous idiosyn...
Adaptive mistranslation accelerates the evolution of fluconazole resistance and...
Weil, Tobias; Santamaría, Rodrigo; Lee, Wanseon; Rung, Johan; Tocci, Noemi; Abbey, Darren; Bezerra, Ana R.; Carreto, Laura; Moura, Gabriela R.Regulated erroneous protein translation (adaptive mistranslation) increases proteome diversity and produces advantageous phenotypic variability in the human pathogen Candida albicans. It also increases fitness in the presence of fluconazole, but the underlying molecular mechanism is not understood. To address this question, we evolved hypermistranslating and wild-type strains in the absence and presence of fluc...
The fungus Candida albicans tolerates ambiguity at multiple codons
Simões, João; Bezerra, Ana R.; Moura, Gabriela R.; Araújo, Hugo; Gut, Ivo; Bayes, Mónica; Santos, Manuel A. S.The ascomycete Candida albicans is a normal resident of the gastrointestinal tract of humans and other warm-blooded animals. It occurs in a broad range of body sites and has high capacity to survive and proliferate in adverse environments with drastic changes in oxygen, carbon dioxide, pH, osmolarity, nutrients, and temperature. Its biology is unique due to flexible reassignment of the leucine CUG codon to seri...
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...
Reversion of a fungal genetic code alteration links proteome instability with g...
Bezerra, Ana R.; Simões, João; Lee, Wanseon; Rung, Johan; Weil, Tobias; Gut, Ivo G.; Gut, Marta; Bayes, Mónica; Rizzetto, Lisa; Cavalieri, DuccioMany fungi restructured their proteomes through incorporation of serine (Ser) at thousands of protein sites coded by the leucine (Leu) CUG codon. How these fungi survived this potentially lethal genetic code alteration and its relevance for their biology are not understood. Interestingly, the human pathogen Candida albicans maintains variable Ser and Leu incorporation levels at CUG sites, suggesting that this a...
Molecular reconstruction of a fungal genetic code alteration
Mateus, Denisa D.; Paredes, João A.; Español, Yaiza; Ribas de Pouplana, Lluís; Moura, Gabriela R.; Santos, Manuel A. S.Fungi of the CTG clade translate the Leu CUG codon as Ser. This genetic code alteration is the only eukaryotic sense-to-sense codon reassignment known to date, is mediated by an ambiguous serine tRNA (tRNACAG(Ser)), exposes unanticipated flexibility of the genetic code and raises major questions about its selection and fixation in this fungal lineage. In particular, the origin of the tRNACAG(Ser) and the evolut...
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, IngridBackground - 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...
Low level genome mistranslations deregulate the transcriptome and translatome a...
Paredes, João A.; Carreto, Laura; Simões, João; Bezerra, Ana R.; Gomes, Ana C.; Santamaria, Rodrigo; Kapushesky, Misha; Moura, Gabriela R.Organisms use highly accurate molecular processes to transcribe their genes and a variety of mRNA quality control and ribosome proofreading mechanisms to maintain intact the fidelity of genetic information flow. Despite this, low level gene translational errors induced by mutations and environmental factors cause neurodegeneration and premature death in mice and mitochondrial disorders in humans. Paradoxically,...