A novel function for fragile X mental retardation protein in translational activation.
Fragile X syndrome, the most frequent form of inherited mental retardation, is due to the absence of Fragile X Mental Retardation Protein (FMRP), an RNA-binding protein involved in several steps of RNA metabolism. To date, two RNA motifs have been found to mediate FMRP/RNA interaction, the G-quartet...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2009-01-01
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| Series: | PLoS Biology |
| Online Access: | http://europepmc.org/articles/PMC2628407?pdf=render |
| _version_ | 1818923502680408064 |
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| author | Elias G Bechara Marie Cecile Didiot Mireille Melko Laetitia Davidovic Mounia Bensaid Patrick Martin Marie Castets Philippe Pognonec Edouard W Khandjian Hervé Moine Barbara Bardoni |
| author_facet | Elias G Bechara Marie Cecile Didiot Mireille Melko Laetitia Davidovic Mounia Bensaid Patrick Martin Marie Castets Philippe Pognonec Edouard W Khandjian Hervé Moine Barbara Bardoni |
| author_sort | Elias G Bechara |
| collection | DOAJ |
| description | Fragile X syndrome, the most frequent form of inherited mental retardation, is due to the absence of Fragile X Mental Retardation Protein (FMRP), an RNA-binding protein involved in several steps of RNA metabolism. To date, two RNA motifs have been found to mediate FMRP/RNA interaction, the G-quartet and the "kissing complex," which both induce translational repression in the presence of FMRP. We show here a new role for FMRP as a positive modulator of translation. FMRP specifically binds Superoxide Dismutase 1 (Sod1) mRNA with high affinity through a novel RNA motif, SoSLIP (Sod1 mRNA Stem Loops Interacting with FMRP), which is folded as three independent stem-loop structures. FMRP induces a structural modification of the SoSLIP motif upon its interaction with it. SoSLIP also behaves as a translational activator whose action is potentiated by the interaction with FMRP. The absence of FMRP results in decreased expression of Sod1. Because it has been observed that brain metabolism of FMR1 null mice is more sensitive to oxidative stress, we propose that the deregulation of Sod1 expression may be at the basis of several traits of the physiopathology of the Fragile X syndrome, such as anxiety, sleep troubles, and autism. |
| first_indexed | 2024-12-20T02:10:27Z |
| format | Article |
| id | doaj.art-f598bb1672cb4de8a9ff507a808421eb |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-12-20T02:10:27Z |
| publishDate | 2009-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-f598bb1672cb4de8a9ff507a808421eb2022-12-21T19:57:05ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852009-01-0171e1610.1371/journal.pbio.1000016A novel function for fragile X mental retardation protein in translational activation.Elias G BecharaMarie Cecile DidiotMireille MelkoLaetitia DavidovicMounia BensaidPatrick MartinMarie CastetsPhilippe PognonecEdouard W KhandjianHervé MoineBarbara BardoniFragile X syndrome, the most frequent form of inherited mental retardation, is due to the absence of Fragile X Mental Retardation Protein (FMRP), an RNA-binding protein involved in several steps of RNA metabolism. To date, two RNA motifs have been found to mediate FMRP/RNA interaction, the G-quartet and the "kissing complex," which both induce translational repression in the presence of FMRP. We show here a new role for FMRP as a positive modulator of translation. FMRP specifically binds Superoxide Dismutase 1 (Sod1) mRNA with high affinity through a novel RNA motif, SoSLIP (Sod1 mRNA Stem Loops Interacting with FMRP), which is folded as three independent stem-loop structures. FMRP induces a structural modification of the SoSLIP motif upon its interaction with it. SoSLIP also behaves as a translational activator whose action is potentiated by the interaction with FMRP. The absence of FMRP results in decreased expression of Sod1. Because it has been observed that brain metabolism of FMR1 null mice is more sensitive to oxidative stress, we propose that the deregulation of Sod1 expression may be at the basis of several traits of the physiopathology of the Fragile X syndrome, such as anxiety, sleep troubles, and autism.http://europepmc.org/articles/PMC2628407?pdf=render |
| spellingShingle | Elias G Bechara Marie Cecile Didiot Mireille Melko Laetitia Davidovic Mounia Bensaid Patrick Martin Marie Castets Philippe Pognonec Edouard W Khandjian Hervé Moine Barbara Bardoni A novel function for fragile X mental retardation protein in translational activation. PLoS Biology |
| title | A novel function for fragile X mental retardation protein in translational activation. |
| title_full | A novel function for fragile X mental retardation protein in translational activation. |
| title_fullStr | A novel function for fragile X mental retardation protein in translational activation. |
| title_full_unstemmed | A novel function for fragile X mental retardation protein in translational activation. |
| title_short | A novel function for fragile X mental retardation protein in translational activation. |
| title_sort | novel function for fragile x mental retardation protein in translational activation |
| url | http://europepmc.org/articles/PMC2628407?pdf=render |
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