5 documents found, page 1 of 1
Codon misreading tRNAs promote tumor growth in mice
Santos, Mafalda; Pereira, Patrícia M.; Varanda, A. Sofia; Carvalho, Joana; Azevedo, Mafalda; Mateus, Denisa D.; Mendes, Nuno; Oliveira, PatríciaDeregulation of tRNAs, aminoacyl-tRNA synthetases and tRNA modifying enzymes are common in cancer, raising the hypothesis that protein synthesis efficiency and accuracy (mistranslation) are compromised in tumors. We show here that human colon tumors and xenograft tumors produced in mice by two epithelial cancer cell lines mistranslate 2- to 4-fold more frequently than normal tissue. To clarify if protein mistra...
Rescue of wild-type E-cadherin expression from nonsense-mutated cancer cells by...
Bordeira-Carriço, Renata; Ferreira, Daniel; Mateus, Denisa D.; Pinheiro, Hugo; Pêgo, Ana Paula; Santos, Manuel A. S.; Oliveira, CarlaHereditary diffuse gastric cancer (HDGC) syndrome, although rare, is highly penetrant at an early age, and is severe and incurable because of ineffective screening tools and therapy. Approximately 45% of HDGC families carry germline CDH1/E-cadherin alterations, 20% of which are nonsense leading to premature protein truncation. Prophylactic gastrectomy is the only recommended approach for all asymptomatic CDH1 m...
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...
The yeast PNC1 longevity gene is up-regulated by mRNA mistranslation
Silva, Raquel M.; Duarte, Iven C. N.; Paredes, João A.; Lima-Costa, Tatiana; Perrot, Michel; Boucherie, Hélian; Goodfellow, Brian J.; Gomes, Ana C.Translation fidelity is critical for protein synthesis and to ensure correct cell functioning. Mutations in the protein synthesis machinery or environmental factors that increase synthesis of mistranslated proteins result in cell death and degeneration and are associated with neurodegenerative diseases, cancer and with an increasing number of mitochondrial disorders. Remarkably, mRNA mistranslation plays critic...
A genetic code alteration is a phenotype diversity generator in the human patho...
Miranda, Isabel; Rocha, Rita; Santos, Maria C.; Mateus, Denisa D.; Moura, Gabriela R.; Carreto, Laura; Santos, Manuel A. S.Background. The discovery of genetic code alterations and expansions in both prokaryotes and eukaryotes abolished the hypothesis of a frozen and universal genetic code and exposed unanticipated flexibility in codon and amino acid assignments. It is now clear that codon identity alterations involve sense and non-sense codons and can occur in organisms with complex genomes and proteomes. However, the biological f...