Expressed pseudogenes in the transcriptional landscape of human cancers

Shanker Kalyana-Sundaram; Chandan Kumar-Sinha; Sunita Shankar; Dan R. Robinson; Yi Mi Wu; Xuhong Cao; Irfan A. Asangani; Vishal Kothari; John R. Prensner; Robert J. Lonigro; Matthew K. Iyer; Terrence Barrette; Achiraman Shanmugam; Saravana M. Dhanasekaran; Nallasivam Palanisamy; Arul M. Chinnaiyan

doi:10.1016/j.cell.2012.04.041

Expressed pseudogenes in the transcriptional landscape of human cancers

Shanker Kalyana-Sundaram, Chandan Kumar-Sinha, Sunita Shankar, Dan R. Robinson, Yi Mi Wu, Xuhong Cao, Irfan A. Asangani, Vishal Kothari, John R. Prensner, Robert J. Lonigro, Matthew K. Iyer, Terrence Barrette, Achiraman Shanmugam, Saravana M. Dhanasekaran, Nallasivam Palanisamy, Arul M. Chinnaiyan^*

^*Corresponding author for this work

Urology

Research output: Contribution to journal › Article › peer-review

230 Scopus citations

Abstract

Pseudogene transcripts can provide a novel tier of gene regulation through generation of endogenous siRNAs or miRNA-binding sites. Characterization of pseudogene expression, however, has remained confined to anecdotal observations due to analytical challenges posed by the extremely close sequence similarity with their counterpart coding genes. Here, we describe a systematic analysis of pseudogene "transcription" from an RNA-Seq resource of 293 samples, representing 13 cancer and normal tissue types, and observe a surprisingly prevalent, genome-wide expression of pseudogenes that could be categorized as ubiquitously expressed or lineage and/or cancer specific. Further, we explore disease subtype specificity and functions of selected expressed pseudogenes. Taken together, we provide evidence that transcribed pseudogenes are a significant contributor to the transcriptional landscape of cells and are positioned to play significant roles in cellular differentiation and cancer progression, especially in light of the recently described ceRNA networks. Our work provides a transcriptome resource that enables high-throughput analyses of pseudogene expression.

Original language	English (US)
Pages (from-to)	1622-1634
Number of pages	13
Journal	Cell
Volume	149
Issue number	7
DOIs	https://doi.org/10.1016/j.cell.2012.04.041
State	Published - Jun 22 2012

Funding

The authors thank Ram-Shankar Mani, Kalpana Ramnarayanan, Joseph Mierwaza, and Sooryanarayana Varambally for technical help and Javed Siddiqui for providing samples. This work was supported, in part, by the National Institutes of Health (R01CA132874), Early Detection Research Network grant UO1 CA111275, Prostate SPORE grant P50CA69568, and the Department of Defense Era of Hope grant BC075023 (A.M.C.). A.M.C. is supported by the Doris Duke Charitable Foundation Clinical Scientist Award and the Prostate Cancer Foundation. A.M.C. is an American Cancer Society Research Professor and A. Alfred Taubman Scholar.

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.cell.2012.04.041

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Kalyana-Sundaram, S., Kumar-Sinha, C., Shankar, S., Robinson, D. R., Wu, Y. M., Cao, X., Asangani, I. A., Kothari, V., Prensner, J. R., Lonigro, R. J., Iyer, M. K., Barrette, T., Shanmugam, A., Dhanasekaran, S. M., Palanisamy, N., & Chinnaiyan, A. M. (2012). Expressed pseudogenes in the transcriptional landscape of human cancers. Cell, 149(7), 1622-1634. https://doi.org/10.1016/j.cell.2012.04.041

@article{145777f7249148d081974f5b8ed3978f,

title = "Expressed pseudogenes in the transcriptional landscape of human cancers",

abstract = "Pseudogene transcripts can provide a novel tier of gene regulation through generation of endogenous siRNAs or miRNA-binding sites. Characterization of pseudogene expression, however, has remained confined to anecdotal observations due to analytical challenges posed by the extremely close sequence similarity with their counterpart coding genes. Here, we describe a systematic analysis of pseudogene {"}transcription{"} from an RNA-Seq resource of 293 samples, representing 13 cancer and normal tissue types, and observe a surprisingly prevalent, genome-wide expression of pseudogenes that could be categorized as ubiquitously expressed or lineage and/or cancer specific. Further, we explore disease subtype specificity and functions of selected expressed pseudogenes. Taken together, we provide evidence that transcribed pseudogenes are a significant contributor to the transcriptional landscape of cells and are positioned to play significant roles in cellular differentiation and cancer progression, especially in light of the recently described ceRNA networks. Our work provides a transcriptome resource that enables high-throughput analyses of pseudogene expression.",

author = "Shanker Kalyana-Sundaram and Chandan Kumar-Sinha and Sunita Shankar and Robinson, {Dan R.} and Wu, {Yi Mi} and Xuhong Cao and Asangani, {Irfan A.} and Vishal Kothari and Prensner, {John R.} and Lonigro, {Robert J.} and Iyer, {Matthew K.} and Terrence Barrette and Achiraman Shanmugam and Dhanasekaran, {Saravana M.} and Nallasivam Palanisamy and Chinnaiyan, {Arul M.}",

note = "Funding Information: The authors thank Ram-Shankar Mani, Kalpana Ramnarayanan, Joseph Mierwaza, and Sooryanarayana Varambally for technical help and Javed Siddiqui for providing samples. This work was supported, in part, by the National Institutes of Health (R01CA132874), Early Detection Research Network grant UO1 CA111275, Prostate SPORE grant P50CA69568, and the Department of Defense Era of Hope grant BC075023 (A.M.C.). A.M.C. is supported by the Doris Duke Charitable Foundation Clinical Scientist Award and the Prostate Cancer Foundation. A.M.C. is an American Cancer Society Research Professor and A. Alfred Taubman Scholar. ",

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doi = "10.1016/j.cell.2012.04.041",

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Kalyana-Sundaram, S, Kumar-Sinha, C, Shankar, S, Robinson, DR, Wu, YM, Cao, X, Asangani, IA, Kothari, V, Prensner, JR, Lonigro, RJ, Iyer, MK, Barrette, T, Shanmugam, A, Dhanasekaran, SM, Palanisamy, N & Chinnaiyan, AM 2012, 'Expressed pseudogenes in the transcriptional landscape of human cancers', Cell, vol. 149, no. 7, pp. 1622-1634. https://doi.org/10.1016/j.cell.2012.04.041

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AU - Kalyana-Sundaram, Shanker

AU - Kumar-Sinha, Chandan

AU - Shankar, Sunita

AU - Robinson, Dan R.

AU - Wu, Yi Mi

AU - Cao, Xuhong

AU - Asangani, Irfan A.

AU - Kothari, Vishal

AU - Prensner, John R.

AU - Lonigro, Robert J.

AU - Iyer, Matthew K.

AU - Barrette, Terrence

AU - Shanmugam, Achiraman

AU - Dhanasekaran, Saravana M.

AU - Palanisamy, Nallasivam

AU - Chinnaiyan, Arul M.

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PY - 2012/6/22

Y1 - 2012/6/22

N2 - Pseudogene transcripts can provide a novel tier of gene regulation through generation of endogenous siRNAs or miRNA-binding sites. Characterization of pseudogene expression, however, has remained confined to anecdotal observations due to analytical challenges posed by the extremely close sequence similarity with their counterpart coding genes. Here, we describe a systematic analysis of pseudogene "transcription" from an RNA-Seq resource of 293 samples, representing 13 cancer and normal tissue types, and observe a surprisingly prevalent, genome-wide expression of pseudogenes that could be categorized as ubiquitously expressed or lineage and/or cancer specific. Further, we explore disease subtype specificity and functions of selected expressed pseudogenes. Taken together, we provide evidence that transcribed pseudogenes are a significant contributor to the transcriptional landscape of cells and are positioned to play significant roles in cellular differentiation and cancer progression, especially in light of the recently described ceRNA networks. Our work provides a transcriptome resource that enables high-throughput analyses of pseudogene expression.

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Expressed pseudogenes in the transcriptional landscape of human cancers

Abstract

Funding

ASJC Scopus subject areas

UN SDGs

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