16 documents found, page 1 of 2
Integration of segmented regression analysis with weighted gene correlation net...
Ferreira, Margarida; Francisco, Stephany; Soares, Ana R.; Nobre, Ana; Pinheiro, Miguel; Reis, Andreia; Neto, Sonya; Rodrigues, Ana João; Sousa, NunoGene expression alterations occurring with aging have been described for a multitude of species, organs, and cell types. However, most of the underlying studies rely on static comparisons of mean gene expression levels between age groups and do not account for the dynamics of gene expression throughout the lifespan. These studies also tend to disregard the pairwise relationships between gene expression profiles...
m5U54 tRNA hypomodification by lack of TRMT2A drives the generation of tRNA-der...
Pereira, Marisa; Ribeiro, Diana R.; Pinheiro, Miguel M.; Ferreira, Margarida; Kellner, Stefanie; Soares, Ana R.Transfer RNA (tRNA) molecules contain various post-transcriptional modifications that are crucial for tRNA stability, translation efficiency, and fidelity. Besides their canonical roles in translation, tRNAs also originate tRNA-derived small RNAs (tsRNAs), a class of small non-coding RNAs with regulatory functions ranging from translation regulation to gene expression control and cellular stress response. Recen...
m5U54 tRNA hypomodification induces the generation of tRNA-derived small RNAs
Pereira, Marisa; Ribeiro, Diana R.; Kellner, Stefanie; Soares, Ana R.Transfer RNAs (tRNAs) are the effector molecules of translation and are also a known source of small non-coding RNAs collectively known as tRNA-derived small RNAs (tsRNAs). tsRNAs have regulatory functions that range from translation regulation to gene expression control and cellular stress response, but what exactly triggers their formation is still under discussion. Both tRNAs and tsRNAs bear several modifica...
Lack of TRMT2A, a tRNA methyltransferase, leads to m5U54 tRNA hypomodification ...
Pereira, Marisa; Ribeiro, Diana R.; Pinheiro, Miguel M.; Ferreira, Margarida; Kellner, Stefanie; Soares, Ana R.Transfer RNAs (tRNAs) are subjected to a wide variety of post-transcriptional modifications to ensure their structural stability, correct folding, and efficient protein decoding. More specifically, modifications in the D- and T-loops of tRNAs are essential for tRNA stability. However, the biological role of the tRNA epitranscriptome in the generation of tRNA-derived small RNA fragments (tsRNAs), a class of smal...
tRNA-modifying enzyme mutations induce codon-specific mistranslation and protei...
Tavares, Joana F.; Davis, Nick K.; Poim, Ana; Reis, Andreia; Kellner, Stefanie; Sousa, Inês; Soares, Ana R.; Moura, Gabriela M. R.; Dedon, Peter C.Protein synthesis rate and accuracy are tightly controlled by the cell and are essential for proteome homoeostasis (proteostasis); however, the full picture of how mRNA translational factors maintain protein synthesis accuracy and co-translational protein folding are far from being fully understood. To address this question, we evaluated the role of 70 yeast tRNA-modifying enzyme genes on protein aggregation an...
Human cells adapt to translational errors by modulating protein synthesis rate ...
Varanda, Ana Sofia; Santos, Mafalda; Soares, Ana R.; Vitorino, Rui; Oliveira, Patrícia; Oliveira, Carla; Santos, Manuel A. S.Deregulation of tRNAs, aminoacyl-tRNA synthetases (aaRS) or tRNA modifying enzymes, increase the level of protein synthesis errors (PSE) and are associated with several diseases, but the cause-effect mechanisms of these pathologies remain elusive. To clarify the role of PSE in human biology, we have engineered a HEK293 cell line to overexpress a wild type (Wt) tRNASer and two tRNASer mutants that misincorporate...
Evidence for lack of direct causality between pain and affective disturbances i...
Guimarães, Marco Rafael Machado; Soares, Ana R.; Cunha, Ana M.; Esteves, Madalena; Borges, Sónia; Magalhães, Ricardo José SilvaChronic pain is frequently accompanied by the manifestation of emotional disturbances and cognitive deficits. While a causality relation between pain and emotional/cognitive disturbances is generally assumed, several observations suggest a temporal dissociation and independent mechanisms. We therefore studied Sprague-Dawley rats that presented a natural resistance to pain manifestation in a neuropathy model (sp...
A fluorescence based sensor assay that monitors general protein aggregation in ...
Pereira, Marisa; Tomé, Diogo; Domingues, Ana S.; Varanda, Ana S.; Paulo, Cristiana; Santos, Manuel A. S.; Soares, Ana R.Protein conformational disorders are characterized by disruption of protein folding and toxic accumulation of protein aggregates. Here we describe a sensitive and simple method to follow and monitor general protein aggregation in human cells. Heat shock protein 27 (HSP27) is an oligomeric small heat shock protein that binds and keeps unfolded proteins in a folding competent state. This high specificity of HSP27...
RUN and FYVE domain-containing protein 4 enhances autophagy and lysosome tether...
Terawaki, Seigo; Camosseto, Voahirana; Prete, Francesca; Wenger, Till; Papadopoulos, Alexia; Rondeau, Christiane; Combes, AlexisAutophagy is a key degradative pathway coordinated by external cues, including starvation, oxidative stress, or pathogen detection. Rare are the molecules known to contribute mechanistically to the regulation of autophagy and expressed specifically in particular environmental contexts or in distinct cell types. Here, we unravel the role of RUN and FYVE domain–containing protein 4 (RUFY4) as a positive molecular...
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...