Expressed pseudogenes in the transcriptional landscape of human cancers.
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.
Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Shanker
S
Kalyana-Sundaram
Chandan
C
Kumar-Sinha
Sunita
S
Shankar
Dan R
DR
Robinson
Yi-Mi
YM
Wu
Xuhong
X
Cao
Irfan A
IA
Asangani
Vishal
V
Kothari
John R
JR
Prensner
Robert J
RJ
Lonigro
Matthew K
MK
Iyer
Terrence
T
Barrette
Achiraman
A
Shanmugam
Saravana M
SM
Dhanasekaran
Nallasivam
N
Palanisamy
Arul M
AM
Chinnaiyan
D000595:Amino Acid Sequence; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics; D011544:Pseudogenes / Q000235:genetics*; D017423:Sequence Analysis, RNA; D059467:Transcriptome