Oligophrenin-1 (OPHN1), a gene involved in X-linked intellectual disability, undergoes RNA editing and alternative splicing during human brain development

Sabina Barresi; Sara Tomaselli; Alekos Athanasiadis; Federica Galeano; Franco Locatelli; Enrico Bertini; Ginevra Zanni; Angela Gallo

doi:10.1371/journal.pone.0091351

Oligophrenin-1 (OPHN1), a gene involved in X-linked intellectual disability, undergoes RNA editing and alternative splicing during human brain development

PLoS One. 2014 Mar 17;9(3):e91351. doi: 10.1371/journal.pone.0091351. eCollection 2014.

Authors

Sabina Barresi¹, Sara Tomaselli², Alekos Athanasiadis³, Federica Galeano², Franco Locatelli⁴, Enrico Bertini¹, Ginevra Zanni¹, Angela Gallo²

Affiliations

¹ Molecular Medicine Laboratory, Neurosciences Department, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
² RNA Editing Laboratory, Oncohaematology Department, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
³ Instituto Gulbenkian de Ciência, Oeiras, Portugal.
⁴ RNA Editing Laboratory, Oncohaematology Department, Bambino Gesù Children's Hospital IRCCS, Rome, Italy; Università di Pavia, Pavia, Italy.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenosine Deaminase / metabolism
Alternative Splicing*
Base Sequence
Brain / embryology
Brain / metabolism*
Cell Line
Cytoskeletal Proteins / genetics*
GTPase-Activating Proteins / genetics*
Gene Expression Regulation, Developmental
Gene Order
Humans
Mental Retardation, X-Linked / embryology
Mental Retardation, X-Linked / genetics*
Mental Retardation, X-Linked / metabolism
Molecular Sequence Data
Nuclear Proteins / genetics*
Nucleic Acid Conformation
Organogenesis / genetics*
RNA Editing*
RNA Isoforms
RNA Precursors / chemistry
RNA Precursors / genetics
RNA-Binding Proteins / metabolism

Substances

Cytoskeletal Proteins
GTPase-Activating Proteins
Nuclear Proteins
OPHN1 protein, human
RNA Isoforms
RNA Precursors
RNA-Binding Proteins
ADARB1 protein, human
Adenosine Deaminase

Grants and funding

This work was supported by an IG grant (n. 13202) to A.G. from AIRC (Associazione Italiana Ricerca sul cancro) and by the special project 5×1000 AIRC to F.L. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.