FRAXE-associated mental retardation protein (FMR2) is an RNA-binding protein with high affinity for G-quartet RNA forming structure
| Autor: | Jozef Gecz, Mireille Melko, Barbara Bardoni, Elias Bechara, Enzo Lalli, Mounia Bensaid, Maria Vincenza Catania, Laetitia Davidovic, Antonio Berretta |
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| Přispěvatelé: | Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Institute of Neurological Sciences (CNR), National Research Council [Italy] (CNR), Department of Chemical Sciences, Università degli studi di Catania [Catania], Oasi Maria SS Institute for Research on Mental Retardation and Brain Aging, Oasi Maria SS Institute, Department of Genetic Medicine Women's and Children's, University of Adelaide |
| Rok vydání: | 2009 |
| Předmět: |
RNA Splicing Factors
Exonic splicing enhancer RNA-binding protein [SDV.BC]Life Sciences [q-bio]/Cellular Biology Biology MESH: Fragile X Mental Retardation Protein Cell Line Fragile X Mental Retardation Protein Mice MESH: Protein Structure Tertiary 03 medical and health sciences Exon Splicing factor 0302 clinical medicine MESH: RNA Genetics Animals Humans MESH: Animals [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology MESH: Cell Nucleus Structures MESH: Mice Cells Cultured 030304 developmental biology 0303 health sciences MESH: Humans MESH: Alternative Splicing Alternative splicing Nuclear Proteins RNA-Binding Proteins Molecular biology Cell Nucleus Structures Protein Structure Tertiary MESH: Cell Line G-Quadruplexes Alternative Splicing MESH: RNA-Binding Proteins RNA splicing RNA [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] MESH: Nuclear Proteins 030217 neurology & neurosurgery MESH: Cells Cultured MESH: G-Quadruplexes Minigene |
| Zdroj: | Nucleic Acids Research Nucleic Acids Research, Oxford University Press, 2009, 37 (4), pp.1269-79. ⟨10.1093/nar/gkn1058⟩ |
| ISSN: | 1362-4962 0305-1048 |
| DOI: | 10.1093/nar/gkn1058 |
| Popis: | International audience; FRAXE is a form of mild to moderate mental retardation due to the silencing of the FMR2 gene. The cellular function of FMR2 protein is presently unknown. By analogy with its homologue AF4, FMR2 was supposed to have a role in transcriptional regulation, but robust evidences supporting this hypothesis are lacking. We observed that FMR2 co-localizes with the splicing factor SC35 in nuclear speckles, the nuclear regions where splicing factors are concentrated, assembled and modified. Similarly to what was reported for splicing factors, blocking splicing or transcription leads to the accumulation of FMR2 in enlarged, rounded speckles. FMR2 is also localized in the nucleolus when splicing is blocked. We show here that FMR2 is able to specifically bind the G-quartet-forming RNA structure with high affinity. Remarkably, in vivo, in the presence of FMR2, the ESE action of the G-quartet situated in mRNA of an alternatively spliced exon of a minigene or of the putative target FMR1 appears reduced. Interestingly, FMR1 is silenced in the fragile X syndrome, another form of mental retardation. All together, our findings strongly suggest that FMR2 is an RNA-binding protein, which might be involved in alternative splicing regulation through an interaction with G-quartet RNA structure. |
| Databáze: | OpenAIRE |
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