title: Expression of Rac1 alternative 3' UTRs is a cell specific mechanism with a function in dendrite outgrowth in cortical neurons.
abstract: The differential expression of mRNAs containing tandem alternative 3' UTRs, achieved by mechanisms of alternative polyadenylation and post-transcriptional regulation, has been correlated with a variety of cellular states. In differentiated cells and brain tissues there is a general use of distal polyadenylation signals, originating mRNAs with longer 3' UTRs, in contrast with proliferating cells and other tissues such as testis, where most mRNAs contain shorter 3' UTRs. Although cell type and state are relevant in many biological processes, how these mechanisms occur in specific brain cell types is still poorly understood. Rac1 is a member of the Rho family of small GTPases with essential roles in multiple cellular processes, including cell differentiation and axonal growth. Here we used different brain cell types and tissues, including oligodendrocytes, microglia, astrocytes, cortical and hippocampal neurons, and optical nerve, to show that classical Rho GTPases express mRNAs with alternative 3' UTRs differently, by gene- and cell- specific mechanisms. In particular, we show that Rac1 originate mRNA isoforms with longer 3' UTRs specifically during neurite growth of cortical, but not hippocampal neurons. Furthermore, we demonstrate that the longest Rac1 3' UTR is necessary for driving the mRNA to the neurites, and also for neurite outgrowth in cortical neurons. Our results indicate that the expression of Rac1 longer 3' UTR is a gene and cell-type specific mechanism in the brain, with a new physiological function in cortical neuron differentiation.
authors.affiliation: Gene Regulation Group, IBMC - Instituto de Biologia Celular e Molecular, Porto, Portugal.
authors.forename: Sandra Oliveira
authors.initials: SO
authors.lastname: Braz
authors.affiliation: Gene Regulation Group, IBMC - Instituto de Biologia Celular e Molecular, Porto, Portugal; Glial Cell Biology Group, IBMC - Instituto de Biologia Celular e Molecular, Porto, Portugal.
authors.forename: Andrea
authors.initials: A
authors.lastname: Cruz
authors.affiliation: Addiction Biology Group, IBMC - Instituto de Biologia Celular e Molecular, Porto, Portugal; Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, Portugal.
authors.forename: Andrea
authors.initials: A
authors.lastname: Lobo
authors.affiliation: Addiction Biology Group, IBMC - Instituto de Biologia Celular e Molecular, Porto, Portugal; Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, Portugal; FMUP-Faculdade de Medicina da Universidade do Porto, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Bravo
authors.affiliation: Addiction Biology Group, IBMC - Instituto de Biologia Celular e Molecular, Porto, Portugal; Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Moreira-Ribeiro
authors.affiliation: Gene Regulation Group, IBMC - Instituto de Biologia Celular e Molecular, Porto, Portugal; Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Pereira-Castro
authors.affiliation: Gene Regulation Group, IBMC - Instituto de Biologia Celular e Molecular, Porto, Portugal; Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, Portugal.
authors.forename: Jaime
authors.initials: J
authors.lastname: Freitas
authors.affiliation: Glial Cell Biology Group, IBMC - Instituto de Biologia Celular e Molecular, Porto, Portugal; Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, Portugal. Electronic address: jrelvas@ibmc.up.pt.
authors.forename: Joao B
authors.initials: JB
authors.lastname: Relvas
authors.affiliation: Addiction Biology Group, IBMC - Instituto de Biologia Celular e Molecular, Porto, Portugal; Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, Portugal. Electronic address: tsummavi@ibmc.up.pt.
authors.forename: Teresa
authors.initials: T
authors.lastname: Summavielle
authors.affiliation: Gene Regulation Group, IBMC - Instituto de Biologia Celular e Molecular, Porto, Portugal; Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, Portugal; ICBAS-Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Portugal. Electronic address: alexandra.moreira@ibmc.up.pt.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Moreira
mesh_terms: D020413:3' Untranslated Regions / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006801:Humans; D016501:Neurites / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D020830:rac1 GTP-Binding Protein / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; C499134:Rac1 protein, rat; D020830:rac1 GTP-Binding Protein
keywords: Alternative polyadenylation; Cortical neuron differentiation; Neurite outgrowth; Rac1