RESUMO
Under environmental stress, such as glucose deprivation, cells form stress granules-the accumulation of cytoplasmic aggregates of repressed translational initiation complexes, proteins, and stalled mRNAs. Recent research implicates stress granules in various diseases, such as neurodegenerative diseases, but the exact regulators responsible for the assembly and disassembly of stress granules are unknown. An important aspect of stress granule formation is the presence of posttranslational modifications on core proteins. One of those modifications is lysine acetylation, which is regulated by either a lysine acetyltransferase or a lysine deacetylase enzyme. This work deciphers the impact of lysine acetylation on an essential protein found in Saccharomyces cerevisiae stress granules, poly(A)-binding protein (Pab1). We demonstrated that an acetylation mimic of the lysine residue in position 131 reduces stress granule formation upon glucose deprivation and other stressors such as ethanol, raffinose, and vanillin. We present genetic evidence that the enzyme Rpd3 is the primary candidate for the deacetylation of Pab1-K131. Further, our electromobility shift assay studies suggest that the acetylation of Pab1-K131 negatively impacts poly(A) RNA binding. Due to the conserved nature of stress granules, therapeutics targeting the activity of lysine acetyltransferases and lysine deacetylase enzymes may be a promising route to modulate stress granule dynamics in the disease state.
Assuntos
Proteínas de Ligação a Poli(A) , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Grânulos de Estresse , Acetilação , Glucose/metabolismo , Lisina/metabolismo , Lisina Acetiltransferases/metabolismo , Proteínas de Ligação a Poli(A)/genética , Proteínas de Ligação a Poli(A)/metabolismo , Processamento de Proteína Pós-Traducional , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismoRESUMO
BACKGROUND: The total number of people affected by dementia worldwide is increasing rapidly. Recent studies provided evidence for the contribution of modifiable risk and protective factors to dementia risk. Although healthcare professionals could play an essential role in informing the general public about the relationship between lifestyle and dementia, it is unclear what they know about this relationship. Therefore, this study assesses the awareness of dementia risk reduction among current and future healthcare professionals. DESIGN AND METHODS: An online survey was carried out among 182 healthcare students from Maastricht University and 20 general practitioners (GPs) and practice nurses in Limburg, The Netherlands. The survey assessed the knowledge about risk and protective factors of dementia and identified needs, wishes and barriers concerning dementia risk reduction strategies. RESULTS: The majority of current (75.0%) and future (81.9%) healthcare professionals indicated that dementia risk reduction is possible. Among students, awareness of cardiovascular risk factors of dementia (e.g., coronary heart disease (44.5%), hypertension (53.8%)) was low. Most participants (>70.0%) would like to receive more information about dementia risk reduction. CONCLUSIONS: The majority of current and future healthcare professionals were aware of the relationship between lifestyle and dementia risk. However, there are still substantial gaps in knowledge regarding individual dementia risk factors. Given the essential role of healthcare professionals in providing lifestyle advice, there is a need to increase awareness by providing educational programs focused on dementia risk reduction.
