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Discovery of CTCF-Sensitive Cis-Spliced Fusion RNAs between Adjacent Genes in Human Prostate Cells

Genes or their encoded products are not expected to mingle with each other unless in some disease situations. In cancer, a frequent mechanism that can produce gene fusions is chromosomal rearrangement. However, recent discoveries of RNA trans-splicing and cis-splicing between adjacent genes (cis-SAG...

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Autores principales: Qin, Fujun, Song, Zhenguo, Babiceanu, Mihaela, Song, Yansu, Facemire, Loryn, Singh, Ritambhara, Adli, Mazhar, Li, Hui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4450057/
https://www.ncbi.nlm.nih.gov/pubmed/25658338
http://dx.doi.org/10.1371/journal.pgen.1005001
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author Qin, Fujun
Song, Zhenguo
Babiceanu, Mihaela
Song, Yansu
Facemire, Loryn
Singh, Ritambhara
Adli, Mazhar
Li, Hui
author_facet Qin, Fujun
Song, Zhenguo
Babiceanu, Mihaela
Song, Yansu
Facemire, Loryn
Singh, Ritambhara
Adli, Mazhar
Li, Hui
author_sort Qin, Fujun
collection PubMed
description Genes or their encoded products are not expected to mingle with each other unless in some disease situations. In cancer, a frequent mechanism that can produce gene fusions is chromosomal rearrangement. However, recent discoveries of RNA trans-splicing and cis-splicing between adjacent genes (cis-SAGe) support for other mechanisms in generating fusion RNAs. In our transcriptome analyses of 28 prostate normal and cancer samples, 30% fusion RNAs on average are the transcripts that contain exons belonging to same-strand neighboring genes. These fusion RNAs may be the products of cis-SAGe, which was previously thought to be rare. To validate this finding and to better understand the phenomenon, we used LNCaP, a prostate cell line as a model, and identified 16 additional cis-SAGe events by silencing transcription factor CTCF and paired-end RNA sequencing. About half of the fusions are expressed at a significant level compared to their parental genes. Silencing one of the in-frame fusions resulted in reduced cell motility. Most out-of-frame fusions are likely to function as non-coding RNAs. The majority of the 16 fusions are also detected in other prostate cell lines, as well as in the 14 clinical prostate normal and cancer pairs. By studying the features associated with these fusions, we developed a set of rules: 1) the parental genes are same-strand-neighboring genes; 2) the distance between the genes is within 30kb; 3) the 5′ genes are actively transcribing; and 4) the chimeras tend to have the second-to-last exon in the 5′ genes joined to the second exon in the 3′ genes. We then randomly selected 20 neighboring genes in the genome, and detected four fusion events using these rules in prostate cancer and non-cancerous cells. These results suggest that splicing between neighboring gene transcripts is a rather frequent phenomenon, and it is not a feature unique to cancer cells.
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spelling pubmed-44500572015-06-23 Discovery of CTCF-Sensitive Cis-Spliced Fusion RNAs between Adjacent Genes in Human Prostate Cells Qin, Fujun Song, Zhenguo Babiceanu, Mihaela Song, Yansu Facemire, Loryn Singh, Ritambhara Adli, Mazhar Li, Hui PLoS Genet Research Article Genes or their encoded products are not expected to mingle with each other unless in some disease situations. In cancer, a frequent mechanism that can produce gene fusions is chromosomal rearrangement. However, recent discoveries of RNA trans-splicing and cis-splicing between adjacent genes (cis-SAGe) support for other mechanisms in generating fusion RNAs. In our transcriptome analyses of 28 prostate normal and cancer samples, 30% fusion RNAs on average are the transcripts that contain exons belonging to same-strand neighboring genes. These fusion RNAs may be the products of cis-SAGe, which was previously thought to be rare. To validate this finding and to better understand the phenomenon, we used LNCaP, a prostate cell line as a model, and identified 16 additional cis-SAGe events by silencing transcription factor CTCF and paired-end RNA sequencing. About half of the fusions are expressed at a significant level compared to their parental genes. Silencing one of the in-frame fusions resulted in reduced cell motility. Most out-of-frame fusions are likely to function as non-coding RNAs. The majority of the 16 fusions are also detected in other prostate cell lines, as well as in the 14 clinical prostate normal and cancer pairs. By studying the features associated with these fusions, we developed a set of rules: 1) the parental genes are same-strand-neighboring genes; 2) the distance between the genes is within 30kb; 3) the 5′ genes are actively transcribing; and 4) the chimeras tend to have the second-to-last exon in the 5′ genes joined to the second exon in the 3′ genes. We then randomly selected 20 neighboring genes in the genome, and detected four fusion events using these rules in prostate cancer and non-cancerous cells. These results suggest that splicing between neighboring gene transcripts is a rather frequent phenomenon, and it is not a feature unique to cancer cells. Public Library of Science 2015-02-06 /pmc/articles/PMC4450057/ /pubmed/25658338 http://dx.doi.org/10.1371/journal.pgen.1005001 Text en © 2015 Qin 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.
spellingShingle Research Article
Qin, Fujun
Song, Zhenguo
Babiceanu, Mihaela
Song, Yansu
Facemire, Loryn
Singh, Ritambhara
Adli, Mazhar
Li, Hui
Discovery of CTCF-Sensitive Cis-Spliced Fusion RNAs between Adjacent Genes in Human Prostate Cells
title Discovery of CTCF-Sensitive Cis-Spliced Fusion RNAs between Adjacent Genes in Human Prostate Cells
title_full Discovery of CTCF-Sensitive Cis-Spliced Fusion RNAs between Adjacent Genes in Human Prostate Cells
title_fullStr Discovery of CTCF-Sensitive Cis-Spliced Fusion RNAs between Adjacent Genes in Human Prostate Cells
title_full_unstemmed Discovery of CTCF-Sensitive Cis-Spliced Fusion RNAs between Adjacent Genes in Human Prostate Cells
title_short Discovery of CTCF-Sensitive Cis-Spliced Fusion RNAs between Adjacent Genes in Human Prostate Cells
title_sort discovery of ctcf-sensitive cis-spliced fusion rnas between adjacent genes in human prostate cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4450057/
https://www.ncbi.nlm.nih.gov/pubmed/25658338
http://dx.doi.org/10.1371/journal.pgen.1005001
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