title: Oligophrenin-1 (OPHN1), a gene involved in X-linked intellectual disability, undergoes RNA editing and alternative splicing during human brain development.
abstract: Oligophrenin-1 (OPHN1) encodes for a Rho-GTPase-activating protein, important for dendritic morphogenesis and synaptic function. Mutations in this gene have been identified in patients with X-linked intellectual disability associated with cerebellar hypoplasia. ADAR enzymes are responsible for A-to-I RNA editing, an essential post-transcriptional RNA modification contributing to transcriptome and proteome diversification. Specifically, ADAR2 activity is essential for brain development and function. Herein, we show that the OPHN1 transcript undergoes post-transcriptional modifications such as A-to-I RNA editing and alternative splicing in human brain and other tissues. We found that OPHN1 editing is detectable already at the 18th week of gestation in human brain with a boost of editing at weeks 20 to 33, concomitantly with OPHN1 expression increase and the appearance of a novel OPHN1 splicing isoform. Our results demonstrate that multiple post-transcriptional events occur on OPHN1, a gene playing an important role in brain function and development.
authors.affiliation: Molecular Medicine Laboratory, Neurosciences Department, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
authors.forename: Sabina
authors.initials: S
authors.lastname: Barresi
authors.affiliation: RNA Editing Laboratory, Oncohaematology Department, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Tomaselli
authors.affiliation: Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: Alekos
authors.initials: A
authors.lastname: Athanasiadis
authors.affiliation: RNA Editing Laboratory, Oncohaematology Department, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Galeano
authors.affiliation: RNA Editing Laboratory, Oncohaematology Department, Bambino Gesù Children's Hospital IRCCS, Rome, Italy; Università di Pavia, Pavia, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.affiliation: Molecular Medicine Laboratory, Neurosciences Department, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Bertini
authors.affiliation: Molecular Medicine Laboratory, Neurosciences Department, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
authors.forename: Ginevra
authors.initials: G
authors.lastname: Zanni
authors.affiliation: RNA Editing Laboratory, Oncohaematology Department, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Gallo
mesh_terms: D000243:Adenosine Deaminase / Q000378:metabolism; D017398:Alternative Splicing; D001483:Base Sequence; D001921:Brain / Q000196:embryology / Q000378:metabolism*; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000235:genetics*; D020690:GTPase-Activating Proteins / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D023061:Gene Order; D006801:Humans; D038901:X-Linked Intellectual Disability / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D009690:Nucleic Acid Conformation; D038081:Organogenesis / Q000235:genetics*; D017393:RNA Editing; D059368:RNA Isoforms; D012322:RNA Precursors / Q000737:chemistry / Q000235:genetics; D016601:RNA-Binding Proteins / Q000378:metabolism
chemical_list: D003598:Cytoskeletal Proteins; D020690:GTPase-Activating Proteins; D009687:Nuclear Proteins; C111952:OPHN1 protein, human; D059368:RNA Isoforms; D012322:RNA Precursors; D016601:RNA-Binding Proteins; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase