The 3' UTR of FMR1 mRNA is a target of miR-101, miR-129-5p and miR-221: implications for the molecular pathology of FXTAS at the synapse.
Identifieur interne : 000734 ( PubMed/Corpus ); précédent : 000733; suivant : 000735The 3' UTR of FMR1 mRNA is a target of miR-101, miR-129-5p and miR-221: implications for the molecular pathology of FXTAS at the synapse.
Auteurs : Samantha Zongaro ; Renate Hukema ; Simona D'Antoni ; Laetitia Davidovic ; Pascal Barbry ; Maria Vincenza Catania ; Rob Willemsen ; Bernard Mari ; Barbara BardoniSource :
- Human molecular genetics [ 1460-2083 ] ; 2013.
English descriptors
- KwdEn :
- 3' Untranslated Regions, Animals, Ataxia (genetics), Ataxia (metabolism), Ataxia (pathology), COS Cells, Cercopithecus aethiops, Disease Models, Animal, Fragile X Mental Retardation Protein (biosynthesis), Fragile X Mental Retardation Protein (genetics), Fragile X Syndrome (genetics), Fragile X Syndrome (metabolism), Fragile X Syndrome (pathology), HeLa Cells, Humans, Mice, MicroRNAs (genetics), MicroRNAs (metabolism), NIH 3T3 Cells, Synapses (genetics), Synapses (metabolism), Synapses (pathology), Tremor (genetics), Tremor (metabolism), Tremor (pathology).
- MESH :
- chemical , biosynthesis : Fragile X Mental Retardation Protein.
- chemical , genetics : Fragile X Mental Retardation Protein, MicroRNAs.
- chemical , metabolism : MicroRNAs.
- chemical : 3' Untranslated Regions.
- genetics : Ataxia, Fragile X Syndrome, Synapses, Tremor.
- metabolism : Ataxia, Fragile X Syndrome, Synapses, Tremor.
- pathology : Ataxia, Fragile X Syndrome, Synapses, Tremor.
- Animals, COS Cells, Cercopithecus aethiops, Disease Models, Animal, HeLa Cells, Humans, Mice, NIH 3T3 Cells.
Abstract
While FMR1 is silenced in Fragile X syndrome (FXS) patients carrying the full mutation, its expression is elevated (2-8 fold) in premutated individuals. These people may develop the Fragile X-associated Tremor/Ataxia syndrome (FXTAS), a late onset neurodegenerative disorder characterized by ataxia and parkinsonism. In addition, people carrying the premutation can be affected by a set of neurological and behavioral disorders during young age. Problems of memory have been detected in these patients as well as in the mouse models for FXTAS. To date little is known concerning the metabolism of FMR1 mRNA, notwithstanding the importance of the finely tuned regulation of the expression of this gene. In the present study, we identified three microRNAs that specifically target the 3' UTR of FMR1 and can modulate its expression throughout the brain particularly at the synapse where their expression is very high. The expression level of miR-221 is reduced in synaptosomal preparations of young FXTAS mice suggesting a general deregulation of transcripts located at the synapse of these mice. By transcriptome analysis, we show here a robust deregulation of the expression levels of genes involved in learning, memory and autistic behavior, Parkinson disease and neurodegeneration. These findings suggest the presence of a synaptopathy in these animals. Interestingly, many of those deregulated mRNAs are target of the same microRNAs that modulate the expression of FMR1 at the synapse.
DOI: 10.1093/hmg/ddt044
PubMed: 23390134
Links to Exploration step
pubmed:23390134Le document en format XML
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Pascal" sort="Barbry, Pascal" uniqKey="Barbry P" first="Pascal" last="Barbry">Pascal Barbry</name></author><author><name sortKey="Catania, Maria Vincenza" sort="Catania, Maria Vincenza" uniqKey="Catania M" first="Maria Vincenza" last="Catania">Maria Vincenza Catania</name></author><author><name sortKey="Willemsen, Rob" sort="Willemsen, Rob" uniqKey="Willemsen R" first="Rob" last="Willemsen">Rob Willemsen</name></author><author><name sortKey="Mari, Bernard" sort="Mari, Bernard" uniqKey="Mari B" first="Bernard" last="Mari">Bernard Mari</name></author><author><name sortKey="Bardoni, Barbara" sort="Bardoni, Barbara" uniqKey="Bardoni B" first="Barbara" last="Bardoni">Barbara Bardoni</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2013">2013</date><idno type="RBID">pubmed:23390134</idno><idno type="pmid">23390134</idno><idno type="doi">10.1093/hmg/ddt044</idno><idno type="wicri:Area/PubMed/Corpus">000734</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000734</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">The 3' UTR of FMR1 mRNA is a target of miR-101, miR-129-5p and miR-221: implications for the molecular pathology of FXTAS at the synapse.</title><author><name sortKey="Zongaro, Samantha" sort="Zongaro, Samantha" uniqKey="Zongaro S" first="Samantha" last="Zongaro">Samantha Zongaro</name><affiliation><nlm:affiliation>CNRS UMR 7275, Institute of Molecular and Cellular Pharmacology, Valbonne Sophia-Antipolis, France.</nlm:affiliation></affiliation></author><author><name sortKey="Hukema, Renate" sort="Hukema, Renate" uniqKey="Hukema R" first="Renate" last="Hukema">Renate Hukema</name></author><author><name sortKey="D Antoni, Simona" sort="D Antoni, Simona" uniqKey="D Antoni S" first="Simona" last="D'Antoni">Simona D'Antoni</name></author><author><name sortKey="Davidovic, Laetitia" sort="Davidovic, Laetitia" uniqKey="Davidovic L" first="Laetitia" last="Davidovic">Laetitia Davidovic</name></author><author><name sortKey="Barbry, Pascal" sort="Barbry, Pascal" uniqKey="Barbry P" first="Pascal" last="Barbry">Pascal Barbry</name></author><author><name sortKey="Catania, Maria Vincenza" sort="Catania, Maria Vincenza" uniqKey="Catania M" first="Maria Vincenza" last="Catania">Maria Vincenza Catania</name></author><author><name sortKey="Willemsen, Rob" sort="Willemsen, Rob" uniqKey="Willemsen R" first="Rob" last="Willemsen">Rob Willemsen</name></author><author><name sortKey="Mari, Bernard" sort="Mari, Bernard" uniqKey="Mari B" first="Bernard" last="Mari">Bernard Mari</name></author><author><name sortKey="Bardoni, Barbara" sort="Bardoni, Barbara" uniqKey="Bardoni B" first="Barbara" last="Bardoni">Barbara Bardoni</name></author></analytic><series><title level="j">Human molecular genetics</title><idno type="eISSN">1460-2083</idno><imprint><date when="2013" type="published">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>3' Untranslated Regions</term><term>Animals</term><term>Ataxia (genetics)</term><term>Ataxia (metabolism)</term><term>Ataxia (pathology)</term><term>COS Cells</term><term>Cercopithecus aethiops</term><term>Disease Models, Animal</term><term>Fragile X Mental Retardation Protein (biosynthesis)</term><term>Fragile X Mental Retardation Protein (genetics)</term><term>Fragile X Syndrome (genetics)</term><term>Fragile X Syndrome (metabolism)</term><term>Fragile X Syndrome (pathology)</term><term>HeLa Cells</term><term>Humans</term><term>Mice</term><term>MicroRNAs (genetics)</term><term>MicroRNAs (metabolism)</term><term>NIH 3T3 Cells</term><term>Synapses (genetics)</term><term>Synapses (metabolism)</term><term>Synapses (pathology)</term><term>Tremor (genetics)</term><term>Tremor (metabolism)</term><term>Tremor (pathology)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Fragile X Mental Retardation Protein</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Fragile X Mental Retardation Protein</term><term>MicroRNAs</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>MicroRNAs</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>3' Untranslated Regions</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Ataxia</term><term>Fragile X Syndrome</term><term>Synapses</term><term>Tremor</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Ataxia</term><term>Fragile X Syndrome</term><term>Synapses</term><term>Tremor</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Ataxia</term><term>Fragile X Syndrome</term><term>Synapses</term><term>Tremor</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>COS Cells</term><term>Cercopithecus aethiops</term><term>Disease Models, Animal</term><term>HeLa Cells</term><term>Humans</term><term>Mice</term><term>NIH 3T3 Cells</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">While FMR1 is silenced in Fragile X syndrome (FXS) patients carrying the full mutation, its expression is elevated (2-8 fold) in premutated individuals. These people may develop the Fragile X-associated Tremor/Ataxia syndrome (FXTAS), a late onset neurodegenerative disorder characterized by ataxia and parkinsonism. In addition, people carrying the premutation can be affected by a set of neurological and behavioral disorders during young age. Problems of memory have been detected in these patients as well as in the mouse models for FXTAS. To date little is known concerning the metabolism of FMR1 mRNA, notwithstanding the importance of the finely tuned regulation of the expression of this gene. In the present study, we identified three microRNAs that specifically target the 3' UTR of FMR1 and can modulate its expression throughout the brain particularly at the synapse where their expression is very high. The expression level of miR-221 is reduced in synaptosomal preparations of young FXTAS mice suggesting a general deregulation of transcripts located at the synapse of these mice. By transcriptome analysis, we show here a robust deregulation of the expression levels of genes involved in learning, memory and autistic behavior, Parkinson disease and neurodegeneration. These findings suggest the presence of a synaptopathy in these animals. Interestingly, many of those deregulated mRNAs are target of the same microRNAs that modulate the expression of FMR1 at the synapse.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">23390134</PMID><DateCreated><Year>2013</Year><Month>04</Month><Day>24</Day></DateCreated><DateCompleted><Year>2013</Year><Month>11</Month><Day>01</Day></DateCompleted><DateRevised><Year>2016</Year><Month>11</Month><Day>22</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1460-2083</ISSN><JournalIssue CitedMedium="Internet"><Volume>22</Volume><Issue>10</Issue><PubDate><Year>2013</Year><Month>May</Month><Day>15</Day></PubDate></JournalIssue><Title>Human molecular genetics</Title><ISOAbbreviation>Hum. Mol. Genet.</ISOAbbreviation></Journal><ArticleTitle>The 3' UTR of FMR1 mRNA is a target of miR-101, miR-129-5p and miR-221: implications for the molecular pathology of FXTAS at the synapse.</ArticleTitle><Pagination><MedlinePgn>1971-82</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1093/hmg/ddt044</ELocationID><Abstract><AbstractText>While FMR1 is silenced in Fragile X syndrome (FXS) patients carrying the full mutation, its expression is elevated (2-8 fold) in premutated individuals. These people may develop the Fragile X-associated Tremor/Ataxia syndrome (FXTAS), a late onset neurodegenerative disorder characterized by ataxia and parkinsonism. In addition, people carrying the premutation can be affected by a set of neurological and behavioral disorders during young age. Problems of memory have been detected in these patients as well as in the mouse models for FXTAS. To date little is known concerning the metabolism of FMR1 mRNA, notwithstanding the importance of the finely tuned regulation of the expression of this gene. In the present study, we identified three microRNAs that specifically target the 3' UTR of FMR1 and can modulate its expression throughout the brain particularly at the synapse where their expression is very high. The expression level of miR-221 is reduced in synaptosomal preparations of young FXTAS mice suggesting a general deregulation of transcripts located at the synapse of these mice. By transcriptome analysis, we show here a robust deregulation of the expression levels of genes involved in learning, memory and autistic behavior, Parkinson disease and neurodegeneration. These findings suggest the presence of a synaptopathy in these animals. Interestingly, many of those deregulated mRNAs are target of the same microRNAs that modulate the expression of FMR1 at the synapse.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Zongaro</LastName><ForeName>Samantha</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>CNRS UMR 7275, Institute of Molecular and Cellular Pharmacology, Valbonne Sophia-Antipolis, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hukema</LastName><ForeName>Renate</ForeName><Initials>R</Initials></Author><Author ValidYN="Y"><LastName>D'Antoni</LastName><ForeName>Simona</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Davidovic</LastName><ForeName>Laetitia</ForeName><Initials>L</Initials></Author><Author ValidYN="Y"><LastName>Barbry</LastName><ForeName>Pascal</ForeName><Initials>P</Initials></Author><Author ValidYN="Y"><LastName>Catania</LastName><ForeName>Maria Vincenza</ForeName><Initials>MV</Initials></Author><Author ValidYN="Y"><LastName>Willemsen</LastName><ForeName>Rob</ForeName><Initials>R</Initials></Author><Author ValidYN="Y"><LastName>Mari</LastName><ForeName>Bernard</ForeName><Initials>B</Initials></Author><Author ValidYN="Y"><LastName>Bardoni</LastName><ForeName>Barbara</ForeName><Initials>B</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>GGP07264</GrantID><Agency>Telethon</Agency><Country>Italy</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2013</Year><Month>02</Month><Day>05</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Hum Mol Genet</MedlineTA><NlmUniqueID>9208958</NlmUniqueID><ISSNLinking>0964-6906</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D020413">3' Untranslated Regions</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C497683">FMR1 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C497684">Fmr1 protein, mouse</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C525709">MIRN221 microRNA, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C546122">MIRN221 microRNA, mouse</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D035683">MicroRNAs</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C541915">Mirn129 microRNA, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>139135-51-6</RegistryNumber><NameOfSubstance UI="D051860">Fragile X Mental Retardation Protein</NameOfSubstance></Chemical></ChemicalList><SupplMeshList><SupplMeshName Type="Disease" UI="C564105">Fragile X Tremor Ataxia Syndrome</SupplMeshName></SupplMeshList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D020413" MajorTopicYN="Y">3' Untranslated Regions</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001259" MajorTopicYN="N">Ataxia</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D019556" MajorTopicYN="N">COS 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MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D035683" MajorTopicYN="N">MicroRNAs</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D041681" MajorTopicYN="N">NIH 3T3 Cells</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013569" MajorTopicYN="N">Synapses</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014202" MajorTopicYN="N">Tremor</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2013</Year><Month>2</Month><Day>8</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2013</Year><Month>2</Month><Day>8</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2013</Year><Month>11</Month><Day>2</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">23390134</ArticleId><ArticleId IdType="pii">ddt044</ArticleId><ArticleId IdType="doi">10.1093/hmg/ddt044</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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