Genome-wide translation control analysis of developing human neurons

Autor(es)

Lins, Erico Moreto ; Oliveira, Natassia Cristina Martins ; Reis, Osvaldo ; Ferrasa, Adriano ; Herai, Roberto ; Muotri, Alysson R. ; Massirer, Katlin Brauer ; Bengtson, Mario Henrique

• Tipo de documento: Artigo Científico
• Fonte: MOLECULAR BRAIN; v. 15, n. 1, p. 15-pg., 2022-06-15.

Resumo

During neuronal differentiation, neuroprogenitor cells become polarized, change shape, extend axons, and form complex dendritic trees. While growing, axons are guided by molecular cues to their final destination, where they establish synaptic connections with other neuronal cells. Several layers of regulation are integrated to control neuronal development properly. Although control of mRNA translation plays an essential role in mammalian gene expression, how it contributes temporarily to the modulation of later stages of neuronal differentiation remains poorly understood. Here, we investigated how translation control affects pathways and processes essential for neuronal maturation, using H9-derived human neuro progenitor cells differentiated into neurons as a model. Through Ribosome Profiling (Riboseq) combined with RNA sequencing (RNAseq) analysis, we found that translation control regulates the expression of critical hub genes. Fundamental synaptic vesicle secretion genes belonging to SNARE complex, Rab family members, and vesicle acidification ATPases are strongly translationally regulated in developing neurons. Translational control also participates in neuronal metabolism modulation, particularly affecting genes involved in the TCA cycle and glutamate synthesis/catabolism. Importantly, we found translation regulation of several critical genes with fundamental roles regulating actin and microtubule cytoskeleton pathways, critical to neurite generation, spine formation, axon guidance, and circuit formation. Our results show that translational control dynamically integrates important signals in neurons, regulating several aspects of its development and biology. (AU)

• Processo FAPESP: 14/21704-9 - Impacto da regulação traducional na diferenciação neuronal
• Beneficiário: Mário Henrique Bengtson
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 14/50897-0 - INCT 2014: Centro de Química Medicinal de Acesso Aberto
• Beneficiário: Katlin Brauer Massirer
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 15/21433-8 - Identificação de vias moleculares reguladas traducionalmente na diferenciação neuronal
• Beneficiário: Érico Luiz Moreto Lins
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto