CACG: A database for comparative analysis of conjoined genes

Kim, Dae-Soo; Kim, Dong-Wook; Kim, Minyoung; Nam, Sang Ki; Choi, Sang-Haeng; Kim, Ryong Nam; Kang, Aram; Kim, Aeri; Park, Hong-Seog

doi:10.1016/j.ygeno.2012.05.005

Cited by 8 publications

(8 citation statements)

References 16 publications

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“…In fact, transcription-induced chimeric RNAs, generated in normal healthy cells, without corresponding genomic rearrangements have been well recognized in the field of genetic research (Akiva, 2005;Fang et al, 2012;Gingeras, 2009;Kim DS, et al, 2007;Kim DS, et al, 2012;Kim P, et al, 2010;Kim RN, et al, 2012;Li et al, 2008;Parra, 2005;Prakash et al, 2010;Thomson et al, 2000;Zhang et al, 2012). However, the existence of transcription-induced chimeric RNAs has not been well appreciated in the cancer research field, where fusion genes play an important role in disease development, progression, and treatment (Edwards, 2010;Mitelman et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…Although the mechanism of formation and the functional roles of chimeric transcripts remain elusive (Kannan et al, 2011;Kim RN, et al, 2012;Parra, 2005), two main mechanisms involved in the generation of transcription-induced chimeric transcripts have been established: 1) Through conjoined genes (two or more closely located genes on the same strand of a chromosome (Kannan et al, 2011;Kim DS, et al, 2012;Kim RN, et al, 2012;Parra, 2005;Prakash et al, 2010), where chimeric transcripts can be generated either by run-off transcription of the upstream gene followed by cis-splicing (Kannan et al, 2011;Prakash et al, 2010;Zhang et al, 2012) or skipping/truncation of the final exon in the upstream gene (Kim RN, et al, 2012); 2) Trans-splicing of RNAs, which generates inter-and intra-chromosomal chimeric transcripts (Fang et al, 2012;Gingeras, 2009;Kannan et al, 2011;Li et al, 2008). The USP9Y and TTTY15 genes are located next to each other in the same direction, meeting the criteria for a conjoined gene.…”

Section: Discussionmentioning

confidence: 99%

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Transcription-Mediated Chimeric RNAs in Prostate Cancer: Time to Revisit Old Hypothesis?

Ren

Zhang

Mao

et al. 2014

OMICS: A Journal of Integrative Biology

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Chromosomal rearrangements and fusion genes play important roles in tumor development and progression. Four high-frequency prostate cancer-specific fusion genes were recently reported in Chinese cases. We attempted to confirm one of the fusion genes, USP9Y-TTTY15, by reverse transcription PCR, but detected the presence of the USP9Y-TTTY15 fusion transcript in cancer samples, nonmalignant prostate tissues, and normal tissues from other organs, demonstrating that it is a transcription-induced chimeric RNA, which is commonly produced in normal tissues. In 105 prostate cancer samples and case-matched adjacent nonmalignant tissues, we determined the expression level of USP9Y-TTTY15 and a previously reported transcription-induced chimeric RNA, SLC45A3-ELK4. The expression levels of both chimeric RNAs vary greatly in cancer and normal cells. USP9Y-TTTY15 expression is neither higher in cancer than adjacent normal tissues, nor correlated with features of advanced prostate cancer. Although the expression level of SLC45A3-ELK4 is higher in cancer than normal cells, and a dramatic increase in its expression from normal to cancer cells is correlated with advanced disease, its expression level in cancer samples alone is not correlated with any clinical parameters. These data show that both chimeric RNAs contribute less to prostate carcinogenesis than previously reported.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Transcription-Mediated Chimeric RNAs in Prostate Cancer: Time to Revisit Old Hypothesis?

Ren

Zhang

Mao

et al. 2014

OMICS: A Journal of Integrative Biology

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“…These transcripts are potentially playing an important role in mammalian development, for example in regulating cell development in human [11] and in other organisms such as chick, quail and mouse [10], [12]. Furthermore, many tandem RNA chimeras were found to be evolutionary conserved [13]. Despite the numerous reports showing the existence of these chimeric transcripts in human, the exact mechanism of their formation is still unknown.…”

Section: Introductionmentioning

confidence: 99%

Tandem RNA Chimeras Contribute to Transcriptome Diversity in Human Population and Are Associated with Intronic Genetic Variants

Greger

Rung

et al. 2014

PLoS ONE

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Chimeric RNAs originating from two or more different genes are known to exist not only in cancer, but also in normal tissues, where they can play a role in human evolution. However, the exact mechanism of their formation is unknown. Here, we use RNA sequencing data from 462 healthy individuals representing 5 human populations to systematically identify and in depth characterize 81 RNA tandem chimeric transcripts, 13 of which are novel. We observe that 6 out of these 81 chimeras have been regarded as cancer-specific. Moreover, we show that a prevalence of long introns at the fusion breakpoint is associated with the chimeric transcripts formation. We also find that tandem RNA chimeras have lower abundances as compared to their partner genes. Finally, by combining our results with genomic data from the same individuals we uncover intronic genetic variants associated with the chimeric RNA formation. Taken together our findings provide an important insight into the chimeric transcripts formation and open new avenues of research into the role of intronic genetic variants in post-transcriptional processing events.

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“…However, more and more chimeric RNAs are being found in non-cancer tissues and cells [17,18,24,27,31–33]. All of the 16 chimeras we studied here could be detected in the normal controls.…”

Section: Discussionmentioning

confidence: 74%

Recurrent cis-SAGe chimeric RNA, D2HGDH-GAL3ST2, in prostate cancer

et al. 2016

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Neighboring genes transcribing in the same direction can form chimeric RNAs via cis-splicing (cis-SAGe). Previously, we reported 16 novel cis-SAGe chimeras in prostate cancer cell lines, and performed in silico validation on 14 pairs of normal and tumor samples from Chinese patients. However, whether these fusions exist in different populations, as well as their clinical implications, remains unclear. To investigate, we developed a bioinformatics pipeline using modified Spliced Transcripts Alignment to a Reference (STAR) to quantify these fusion RNAs simultaneously in silico. From RNA-Seq data of 100 paired normal and prostate cancer samples from TCGA, we find that most fusions are not specific to cancer. However, D2HGDH-GAL3ST2 is more frequently seen in cancer samples, and seems to be enriched in the African American group. Further validation with our own collection as well as from commercial sources did not detect this fusion RNA in 29 normal prostate samples, but in 19 of 93 prostate cancer samples. It is more frequently detected in late stage cancer, suggesting a role in cancer progression. Consistently, silencing this fusion resulted in dramatic reduction of cell proliferation rate and cell motility.

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CACG: A database for comparative analysis of conjoined genes

Cited by 8 publications

References 16 publications

Transcription-Mediated Chimeric RNAs in Prostate Cancer: Time to Revisit Old Hypothesis?

Transcription-Mediated Chimeric RNAs in Prostate Cancer: Time to Revisit Old Hypothesis?

Tandem RNA Chimeras Contribute to Transcriptome Diversity in Human Population and Are Associated with Intronic Genetic Variants

Recurrent cis-SAGe chimeric RNA, D2HGDH-GAL3ST2, in prostate cancer

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