Dra. Graciela L. Boccaccio
Jefa de Laboratorio
Biología Celular del RNA Versión en español
Subject
Regulation of gene expression involves mRNA control in the cytoplasm and we focus on the role of membraneless organelles (MLOs) that contain repressed mRNAs. We investigate how specific MLOs respond to cellular cues and contribute to diverse cellular responses.
Approach
Translational regulation is linked to the formation of specific membraneless organelles (MLO) that condense in the cytosol to store repressed mRNAs. Processing Bodies (PBs) and Stress Granules (SGs), conserved from yeasts to mammals, are among the first examples. The assembly of these mRNA-containing bodies is conceptualized as a phase-demixing process, which is driven by multiple weak intermolecular interactions. While considerable progress on the biophysical principles of MLO formation has been achieved, we approach the subject from a cellular biology perspective to study how MLO are regulated by specific cellular cues and intracellular dynamics.
Advances
Using different cellular models, including primary rodent neurons, as well as insect and mammalian cell lines, we identified several of the first reported SG components and discovered novel MLOs associated to synapses, where numerous messenger RNAs are regulated by synaptic activity. Similar to PBs and SGs, these synaptic RNA-bodies dissolve upon specific stimuli thereby releasing transcripts to allow their translation (Thomas et al. 2005; Baez and Boccaccio, 2005; Thomas et al., 2009; Baez et al., 2011; Luchelli et al., 2015). In addition, we demonstrate the participation of active transport driven by anterograde and retrograde molecular motors in the assembly and dissolution of SGs and PBs (Loschi et al 2009). More recently, we found that MLOs formed by the translational regulator Smaug –which were discovered at our laboratory and are conserved from fly to human- respond to changes in energetic metabolism and affects mitochondrial function (Bruzzone et al.,2020; Fernandez-Alvarez et al., 2020)
Regulation of gene expression involves mRNA control in the cytoplasm and we focus on the role of membraneless organelles (MLOs) that contain repressed mRNAs. We investigate how specific MLOs respond to cellular cues and contribute to diverse cellular responses.
Approach
Translational regulation is linked to the formation of specific membraneless organelles (MLO) that condense in the cytosol to store repressed mRNAs. Processing Bodies (PBs) and Stress Granules (SGs), conserved from yeasts to mammals, are among the first examples. The assembly of these mRNA-containing bodies is conceptualized as a phase-demixing process, which is driven by multiple weak intermolecular interactions. While considerable progress on the biophysical principles of MLO formation has been achieved, we approach the subject from a cellular biology perspective to study how MLO are regulated by specific cellular cues and intracellular dynamics.
Advances
Using different cellular models, including primary rodent neurons, as well as insect and mammalian cell lines, we identified several of the first reported SG components and discovered novel MLOs associated to synapses, where numerous messenger RNAs are regulated by synaptic activity. Similar to PBs and SGs, these synaptic RNA-bodies dissolve upon specific stimuli thereby releasing transcripts to allow their translation (Thomas et al. 2005; Baez and Boccaccio, 2005; Thomas et al., 2009; Baez et al., 2011; Luchelli et al., 2015). In addition, we demonstrate the participation of active transport driven by anterograde and retrograde molecular motors in the assembly and dissolution of SGs and PBs (Loschi et al 2009). More recently, we found that MLOs formed by the translational regulator Smaug –which were discovered at our laboratory and are conserved from fly to human- respond to changes in energetic metabolism and affects mitochondrial function (Bruzzone et al.,2020; Fernandez-Alvarez et al., 2020)