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Fusion transcript loci share many genomic features with non-fusion loci

BACKGROUND: Fusion transcripts are found in many tissues and have the potential to create novel functional products. Here, we investigate the genomic sequences around fusion junctions to better understand the transcriptional mechanisms mediating fusion transcription/splicing. We analyzed data from p...

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Autores principales: Lai, John, An, Jiyuan, Seim, Inge, Walpole, Carina, Hoffman, Andrea, Moya, Leire, Srinivasan, Srilakshmi, Perry-Keene, Joanna L., Wang, Chenwei, Lehman, Melanie L., Nelson, Colleen C., Clements, Judith A., Batra, Jyotsna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4667522/
https://www.ncbi.nlm.nih.gov/pubmed/26626734
http://dx.doi.org/10.1186/s12864-015-2235-4
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author Lai, John
An, Jiyuan
Seim, Inge
Walpole, Carina
Hoffman, Andrea
Moya, Leire
Srinivasan, Srilakshmi
Perry-Keene, Joanna L.
Wang, Chenwei
Lehman, Melanie L.
Nelson, Colleen C.
Clements, Judith A.
Batra, Jyotsna
author_facet Lai, John
An, Jiyuan
Seim, Inge
Walpole, Carina
Hoffman, Andrea
Moya, Leire
Srinivasan, Srilakshmi
Perry-Keene, Joanna L.
Wang, Chenwei
Lehman, Melanie L.
Nelson, Colleen C.
Clements, Judith A.
Batra, Jyotsna
author_sort Lai, John
collection PubMed
description BACKGROUND: Fusion transcripts are found in many tissues and have the potential to create novel functional products. Here, we investigate the genomic sequences around fusion junctions to better understand the transcriptional mechanisms mediating fusion transcription/splicing. We analyzed data from prostate (cancer) cells as previous studies have shown extensively that these cells readily undergo fusion transcription. RESULTS: We used the FusionMap program to identify high-confidence fusion transcripts from RNAseq data. The RNAseq datasets were from our (N = 8) and other (N = 14) clinical prostate tumors with adjacent non-cancer cells, and from the LNCaP prostate cancer cell line that were mock-, androgen- (DHT), and anti-androgen- (bicalutamide, enzalutamide) treated. In total, 185 fusion transcripts were identified from all RNAseq datasets. The majority (76 %) of these fusion transcripts were ‘read-through chimeras’ derived from adjacent genes in the genome. Characterization of sequences at fusion loci were carried out using a combination of the FusionMap program, custom Perl scripts, and the RNAfold program. Our computational analysis indicated that most fusion junctions (76 %) use the consensus GT-AG intron donor-acceptor splice site, and most fusion transcripts (85 %) maintained the open reading frame. We assessed whether parental genes of fusion transcripts have the potential to form complementary base pairing between parental genes which might bring them into physical proximity. Our computational analysis of sequences flanking fusion junctions at parental loci indicate that these loci have a similar propensity as non-fusion loci to hybridize. The abundance of repetitive sequences at fusion and non-fusion loci was also investigated given that SINE repeats are involved in aberrant gene transcription. We found few instances of repetitive sequences at both fusion and non-fusion junctions. Finally, RT-qPCR was performed on RNA from both clinical prostate tumors and adjacent non-cancer cells (N = 7), and LNCaP cells treated as above to validate the expression of seven fusion transcripts and their respective parental genes. We reveal that fusion transcript expression is similar to the expression of parental genes. CONCLUSIONS: Fusion transcripts maintain the open reading frame, and likely use the same transcriptional machinery as non-fusion transcripts as they share many genomic features at splice/fusion junctions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-2235-4) contains supplementary material, which is available to authorized users.
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spelling pubmed-46675222015-12-03 Fusion transcript loci share many genomic features with non-fusion loci Lai, John An, Jiyuan Seim, Inge Walpole, Carina Hoffman, Andrea Moya, Leire Srinivasan, Srilakshmi Perry-Keene, Joanna L. Wang, Chenwei Lehman, Melanie L. Nelson, Colleen C. Clements, Judith A. Batra, Jyotsna BMC Genomics Research Article BACKGROUND: Fusion transcripts are found in many tissues and have the potential to create novel functional products. Here, we investigate the genomic sequences around fusion junctions to better understand the transcriptional mechanisms mediating fusion transcription/splicing. We analyzed data from prostate (cancer) cells as previous studies have shown extensively that these cells readily undergo fusion transcription. RESULTS: We used the FusionMap program to identify high-confidence fusion transcripts from RNAseq data. The RNAseq datasets were from our (N = 8) and other (N = 14) clinical prostate tumors with adjacent non-cancer cells, and from the LNCaP prostate cancer cell line that were mock-, androgen- (DHT), and anti-androgen- (bicalutamide, enzalutamide) treated. In total, 185 fusion transcripts were identified from all RNAseq datasets. The majority (76 %) of these fusion transcripts were ‘read-through chimeras’ derived from adjacent genes in the genome. Characterization of sequences at fusion loci were carried out using a combination of the FusionMap program, custom Perl scripts, and the RNAfold program. Our computational analysis indicated that most fusion junctions (76 %) use the consensus GT-AG intron donor-acceptor splice site, and most fusion transcripts (85 %) maintained the open reading frame. We assessed whether parental genes of fusion transcripts have the potential to form complementary base pairing between parental genes which might bring them into physical proximity. Our computational analysis of sequences flanking fusion junctions at parental loci indicate that these loci have a similar propensity as non-fusion loci to hybridize. The abundance of repetitive sequences at fusion and non-fusion loci was also investigated given that SINE repeats are involved in aberrant gene transcription. We found few instances of repetitive sequences at both fusion and non-fusion junctions. Finally, RT-qPCR was performed on RNA from both clinical prostate tumors and adjacent non-cancer cells (N = 7), and LNCaP cells treated as above to validate the expression of seven fusion transcripts and their respective parental genes. We reveal that fusion transcript expression is similar to the expression of parental genes. CONCLUSIONS: Fusion transcripts maintain the open reading frame, and likely use the same transcriptional machinery as non-fusion transcripts as they share many genomic features at splice/fusion junctions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-2235-4) contains supplementary material, which is available to authorized users. BioMed Central 2015-12-01 /pmc/articles/PMC4667522/ /pubmed/26626734 http://dx.doi.org/10.1186/s12864-015-2235-4 Text en © Lai et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Lai, John
An, Jiyuan
Seim, Inge
Walpole, Carina
Hoffman, Andrea
Moya, Leire
Srinivasan, Srilakshmi
Perry-Keene, Joanna L.
Wang, Chenwei
Lehman, Melanie L.
Nelson, Colleen C.
Clements, Judith A.
Batra, Jyotsna
Fusion transcript loci share many genomic features with non-fusion loci
title Fusion transcript loci share many genomic features with non-fusion loci
title_full Fusion transcript loci share many genomic features with non-fusion loci
title_fullStr Fusion transcript loci share many genomic features with non-fusion loci
title_full_unstemmed Fusion transcript loci share many genomic features with non-fusion loci
title_short Fusion transcript loci share many genomic features with non-fusion loci
title_sort fusion transcript loci share many genomic features with non-fusion loci
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4667522/
https://www.ncbi.nlm.nih.gov/pubmed/26626734
http://dx.doi.org/10.1186/s12864-015-2235-4
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