RESUMO
The protein kinase Gcn2 is a central transducer of nutritional stress signaling important for stress adaptation by normal cells and the survival of cancer cells. In response to nutrient deprivation, Gcn2 phosphorylates eIF2α, thereby repressing general translation while enhancing translation of specific mRNAs with upstream ORFs (uORFs) situated in their 5'-leader regions. Here we performed genome-wide measurements of mRNA translation during histidine starvation in fission yeast Schizosaccharomyces pombe. Polysome analyses were combined with microarray measurements to identify gene transcripts whose translation was up-regulated in response to the stress in a Gcn2-dependent manner. We determined that translation is reprogrammed to enhance RNA metabolism and chromatin regulation and repress ribosome synthesis. Interestingly, translation of intron-containing mRNAs was up-regulated. The products of the regulated genes include additional eIF2α kinase Hri2 amplifying the stress signaling and Gcn5 histone acetyl transferase and transcription factors, together altering genome-wide transcription. Unique dipeptide-coding uORFs and nucleotide motifs, such as '5'-UGA(C/G)GG-3', are found in 5' leader regions of regulated genes and shown to be responsible for translational control.
Assuntos
Motivos de Nucleotídeos , Proteínas Serina-Treonina Quinases/metabolismo , RNA Mensageiro/metabolismo , Proteínas de Schizosaccharomyces pombe/metabolismo , Schizosaccharomyces/enzimologia , Acetiltransferases/metabolismo , Regulação Fúngica da Expressão Gênica , Histidina/metabolismo , Fases de Leitura Aberta , Processamento de Proteína Pós-Traducional , Schizosaccharomyces/genética , eIF-2 Quinase/metabolismoRESUMO
Public health and healthcare professionals perform a wide variety of services for their communities, and serve in important and often overlapping roles, particularly in rural communities. In this qualitative study, public health practitioners in Kansas were asked about their perceptions of barriers to public health and vulnerable people in their communities. Participants from across Kansas were interviewed via teleconferencing, telephone, or email, and emergent themes were identified using qualitative thematic analysis. While asked about public health specifically, during interviews, many participants discussed barriers to healthcare as well. The top barriers to effective public health practice identified in this study were funding, education, accessibility, and affordability. Others included politics, transportation, and the need to expand Medicare and Medicaid. The populations believed most vulnerable in their communities were community members living in poverty, elderly people, and other marginalized populations. Our findings suggest public health practitioners in Kansas observe a lack of understanding and knowledge in their communities about public health, along with the recognition that a lack of accessibility and affordability to health services are barriers to effective public health practice.