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Changes in expression of the long non-coding RNA FMR4 associate with altered gene expression during differentiation of human neural precursor cells
CGG repeat expansions in the Fragile X mental retardation 1 (FMR1) gene are responsible for a family of associated disorders characterized by either intellectual disability and autism Fragile X Syndrome (FXS), or adult-onset neurodegeneration Fragile X-associated Tremor/Ataxia Syndrome. However, the...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4530595/ https://www.ncbi.nlm.nih.gov/pubmed/26322075 http://dx.doi.org/10.3389/fgene.2015.00263 |
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author | Peschansky, Veronica J. Pastori, Chiara Zeier, Zane Motti, Dario Wentzel, Katya Velmeshev, Dmitry Magistri, Marco Bixby, John L. Lemmon, Vance P. Silva, José P. Wahlestedt, Claes |
author_facet | Peschansky, Veronica J. Pastori, Chiara Zeier, Zane Motti, Dario Wentzel, Katya Velmeshev, Dmitry Magistri, Marco Bixby, John L. Lemmon, Vance P. Silva, José P. Wahlestedt, Claes |
author_sort | Peschansky, Veronica J. |
collection | PubMed |
description | CGG repeat expansions in the Fragile X mental retardation 1 (FMR1) gene are responsible for a family of associated disorders characterized by either intellectual disability and autism Fragile X Syndrome (FXS), or adult-onset neurodegeneration Fragile X-associated Tremor/Ataxia Syndrome. However, the FMR1 locus is complex and encodes several long non-coding RNAs, whose expression is altered by repeat expansion mutations. The role of these lncRNAs is thus far unknown; therefore we investigated the functionality of FMR4, which we previously identified. “Full”-length expansions of the FMR1 triplet repeat cause silencing of both FMR1 and FMR4, thus we are interested in potential loss-of-function that may add to phenotypic manifestation of FXS. Since the two transcripts do not exhibit cis-regulation of one another, we examined the potential for FMR4 to regulate target genes at distal genomic loci using gene expression microarrays. We identified FMR4-responsive genes, including the methyl-CpG-binding domain protein 4 (MBD4). Furthermore, we found that in differentiating human neural precursor cells, FMR4 expression is developmentally regulated in opposition to expression of both FMR1 (which is expected to share a bidirectional promoter with FMR4) and MBD4. We therefore propose that FMR4’s function is as a gene-regulatory lncRNA and that this transcript may function in normal development. Closer examination of FMR4 increases our understanding of the role of regulatory lncRNA and the consequences of FMR1 repeat expansions. |
format | Online Article Text |
id | pubmed-4530595 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-45305952015-08-28 Changes in expression of the long non-coding RNA FMR4 associate with altered gene expression during differentiation of human neural precursor cells Peschansky, Veronica J. Pastori, Chiara Zeier, Zane Motti, Dario Wentzel, Katya Velmeshev, Dmitry Magistri, Marco Bixby, John L. Lemmon, Vance P. Silva, José P. Wahlestedt, Claes Front Genet Genetics CGG repeat expansions in the Fragile X mental retardation 1 (FMR1) gene are responsible for a family of associated disorders characterized by either intellectual disability and autism Fragile X Syndrome (FXS), or adult-onset neurodegeneration Fragile X-associated Tremor/Ataxia Syndrome. However, the FMR1 locus is complex and encodes several long non-coding RNAs, whose expression is altered by repeat expansion mutations. The role of these lncRNAs is thus far unknown; therefore we investigated the functionality of FMR4, which we previously identified. “Full”-length expansions of the FMR1 triplet repeat cause silencing of both FMR1 and FMR4, thus we are interested in potential loss-of-function that may add to phenotypic manifestation of FXS. Since the two transcripts do not exhibit cis-regulation of one another, we examined the potential for FMR4 to regulate target genes at distal genomic loci using gene expression microarrays. We identified FMR4-responsive genes, including the methyl-CpG-binding domain protein 4 (MBD4). Furthermore, we found that in differentiating human neural precursor cells, FMR4 expression is developmentally regulated in opposition to expression of both FMR1 (which is expected to share a bidirectional promoter with FMR4) and MBD4. We therefore propose that FMR4’s function is as a gene-regulatory lncRNA and that this transcript may function in normal development. Closer examination of FMR4 increases our understanding of the role of regulatory lncRNA and the consequences of FMR1 repeat expansions. Frontiers Media S.A. 2015-08-10 /pmc/articles/PMC4530595/ /pubmed/26322075 http://dx.doi.org/10.3389/fgene.2015.00263 Text en Copyright © 2015 Peschansky, Pastori, Zeier, Motti, Wentzel, Velmeshev, Magistri, Bixby, Lemmon, Silva and Wahlestedt. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Peschansky, Veronica J. Pastori, Chiara Zeier, Zane Motti, Dario Wentzel, Katya Velmeshev, Dmitry Magistri, Marco Bixby, John L. Lemmon, Vance P. Silva, José P. Wahlestedt, Claes Changes in expression of the long non-coding RNA FMR4 associate with altered gene expression during differentiation of human neural precursor cells |
title | Changes in expression of the long non-coding RNA FMR4 associate with altered gene expression during differentiation of human neural precursor cells |
title_full | Changes in expression of the long non-coding RNA FMR4 associate with altered gene expression during differentiation of human neural precursor cells |
title_fullStr | Changes in expression of the long non-coding RNA FMR4 associate with altered gene expression during differentiation of human neural precursor cells |
title_full_unstemmed | Changes in expression of the long non-coding RNA FMR4 associate with altered gene expression during differentiation of human neural precursor cells |
title_short | Changes in expression of the long non-coding RNA FMR4 associate with altered gene expression during differentiation of human neural precursor cells |
title_sort | changes in expression of the long non-coding rna fmr4 associate with altered gene expression during differentiation of human neural precursor cells |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4530595/ https://www.ncbi.nlm.nih.gov/pubmed/26322075 http://dx.doi.org/10.3389/fgene.2015.00263 |
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