Quantitative Nucleotide Level Analysis of Regulation of Translation in Response to Depolarization of Cultured Neural Cells
Year: 2017
Type: article
Abstract: Studies on regulation of gene expression have contributed substantially to understanding mechanisms for the long-term activity-dependent alterations in neural connectivity that are thought to mediate learning and memory. Most of these studies, however, have focused on the regulation of mRNA transcription. Here, we utilized high-throughput sequencing coupled with ribosome footprinting to globally characterize the regulation of translation in primary mixed neuronal-glial cultures in response to sustained depolarization. We identified substantial and complex regulation of translation, with many transcripts demonstrating changes in ribosomal occupancy independent of transcriptional changes. We also examined sequence-based mechanisms that might regulate changes in translation in response to depolarization. We found that these are partially mediated by features in the mRNA sequence-notably upstream open reading frames and secondary structure in the 5' untranslated region-both of which predict downregulation in response to depolarization. Translationally regulated transcripts are also more likely to be targets of FMRP and include genes implicated in autism in humans. Our findings support the idea that control of mRNA translation plays an important role in response to neural activity across the genome.
Institution: Washington University in St. Louis
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
Funders: Institute of Clinical and Translational Sciences, Children's Discovery Institute, National Alliance for Research on Schizophrenia and Depression, Alvin J. Siteman Cancer Center, Georgia Clinical and Translational Science Alliance, National Institutes of Health, National Institute of Mental Health, National Institute on Drug Abuse, National Cancer Institute, National Center for Advancing Translational Sciences
Awards: G1114310655, G1186758267, G1485266116, G2052854178, G299873027, Washington University Institute of Clinical and Translational Sciences, DEVELOPMENT OF A NOVEL APPROACH TO STUDY ALTERNATIVE TRANSLATION IN THE CNS, G7647900390, TRANSLATION PROFILING AND NANOSCALE LOCALIZATION OF SYNAPTIC TRANSCRIPTS, G8242737674, G9000115080, G9000319192, Cancer Center Support Grant
OpenAlex ID: W2581657177