A Novel RNA Transcript with Antiapoptotic Function Is Silenced in Fragile X Syndrome

Several genome-wide transcriptomics efforts have shown that a large percentage of the mammalian genome is transcribed into RNAs, however, only a small percentage (1–2%) of these RNAs is translated into proteins. Currently there is an intense interest in characterizing the function of the different c...

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Main Authors:	Khalil, Ahmad M., Faghihi, Mohammad Ali, Modarresi, Farzaneh, Brothers, Shaun P., Wahlestedt, Claes
Format:	Online
Language:	English
Published:	Public Library of Science 2008
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2194623/

id	pubmed-2194623
recordtype	oai_dc
spelling	pubmed-21946232008-01-23 A Novel RNA Transcript with Antiapoptotic Function Is Silenced in Fragile X Syndrome Khalil, Ahmad M. Faghihi, Mohammad Ali Modarresi, Farzaneh Brothers, Shaun P. Wahlestedt, Claes Research Article Several genome-wide transcriptomics efforts have shown that a large percentage of the mammalian genome is transcribed into RNAs, however, only a small percentage (1–2%) of these RNAs is translated into proteins. Currently there is an intense interest in characterizing the function of the different classes of noncoding RNAs and their relevance to human disease. Using genomic approaches we discovered FMR4, a primate-specific noncoding RNA transcript (2.4 kb) that resides upstream and likely shares a bidirectional promoter with FMR1. FMR4 is a product of RNA polymerase II and has a similar half-life to FMR1. The CGG expansion in the 5′ UTR of FMR1 appears to affect transcription in both directions as we found FMR4, similar to FMR1, to be silenced in fragile X patients and up-regulated in premutation carriers. Knockdown of FMR4 by several siRNAs did not affect FMR1 expression, nor vice versa, suggesting that FMR4 is not a direct regulatory transcript for FMR1. However, FMR4 markedly affected human cell proliferation in vitro; siRNAs knockdown of FMR4 resulted in alterations in the cell cycle and increased apoptosis, while the overexpression of FMR4 caused an increase in cell proliferation. Collectively, our results demonstrate an antiapoptotic function of FMR4 and provide evidence that a well-studied genomic locus can show unexpected functional complexity. It cannot be excluded that altered FMR4 expression might contribute to aspects of the clinical presentation of fragile X syndrome and/or related disorders. Public Library of Science 2008-01-23 /pmc/articles/PMC2194623/ /pubmed/18213394 http://dx.doi.org/10.1371/journal.pone.0001486 Text en Khalil et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Khalil, Ahmad M. Faghihi, Mohammad Ali Modarresi, Farzaneh Brothers, Shaun P. Wahlestedt, Claes
spellingShingle	Khalil, Ahmad M. Faghihi, Mohammad Ali Modarresi, Farzaneh Brothers, Shaun P. Wahlestedt, Claes A Novel RNA Transcript with Antiapoptotic Function Is Silenced in Fragile X Syndrome
author_facet	Khalil, Ahmad M. Faghihi, Mohammad Ali Modarresi, Farzaneh Brothers, Shaun P. Wahlestedt, Claes
author_sort	Khalil, Ahmad M.
title	A Novel RNA Transcript with Antiapoptotic Function Is Silenced in Fragile X Syndrome
title_short	A Novel RNA Transcript with Antiapoptotic Function Is Silenced in Fragile X Syndrome
title_full	A Novel RNA Transcript with Antiapoptotic Function Is Silenced in Fragile X Syndrome
title_fullStr	A Novel RNA Transcript with Antiapoptotic Function Is Silenced in Fragile X Syndrome
title_full_unstemmed	A Novel RNA Transcript with Antiapoptotic Function Is Silenced in Fragile X Syndrome
title_sort	novel rna transcript with antiapoptotic function is silenced in fragile x syndrome
description	Several genome-wide transcriptomics efforts have shown that a large percentage of the mammalian genome is transcribed into RNAs, however, only a small percentage (1–2%) of these RNAs is translated into proteins. Currently there is an intense interest in characterizing the function of the different classes of noncoding RNAs and their relevance to human disease. Using genomic approaches we discovered FMR4, a primate-specific noncoding RNA transcript (2.4 kb) that resides upstream and likely shares a bidirectional promoter with FMR1. FMR4 is a product of RNA polymerase II and has a similar half-life to FMR1. The CGG expansion in the 5′ UTR of FMR1 appears to affect transcription in both directions as we found FMR4, similar to FMR1, to be silenced in fragile X patients and up-regulated in premutation carriers. Knockdown of FMR4 by several siRNAs did not affect FMR1 expression, nor vice versa, suggesting that FMR4 is not a direct regulatory transcript for FMR1. However, FMR4 markedly affected human cell proliferation in vitro; siRNAs knockdown of FMR4 resulted in alterations in the cell cycle and increased apoptosis, while the overexpression of FMR4 caused an increase in cell proliferation. Collectively, our results demonstrate an antiapoptotic function of FMR4 and provide evidence that a well-studied genomic locus can show unexpected functional complexity. It cannot be excluded that altered FMR4 expression might contribute to aspects of the clinical presentation of fragile X syndrome and/or related disorders.
publisher	Public Library of Science
publishDate	2008
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2194623/
_version_	1611431592937390080

A Novel RNA Transcript with Antiapoptotic Function Is Silenced in Fragile X Syndrome

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