Functional evidence of post-transcriptional regulation by pseudogenes

• Published in: Biochimie Vol. 93; no. 11; pp. 1916 - 1921
• Main Authors: Muro, Enrique M., Mah, Nancy, Andrade-Navarro, Miguel A.
• Format: Journal Article
• Language: English
• Published: France Elsevier B.V 01-11-2011
• Subjects: Animals; Disease - genetics; Evolution; Evolution, Molecular; Gene Expression Regulation; Genomics; Humans; Mice; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Natural antisense transcripts; ncRNA; Pseudogenes; Pseudogenes - genetics; RNA Processing, Post-Transcriptional - genetics; RNA Stability - genetics; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; siRNA; Transcription, Genetic; miRNA; siRNA; Pseudogenes; ncRNA; Natural antisense transcripts
• ISSN: 0300-9084; 1638-6183
• DOI: 10.1016/j.biochi.2011.07.024

Pseudogenes have been mainly considered as functionless evolutionary relics since their discovery in 1977. However, multiple mechanisms of pseudogene functionality have been proposed both at the transcriptional and post-transcriptional level. This review focuses on the role of pseudogenes as post-transcriptional regulators. Two lines of research have recently presented strong evidence of their potential function as post-transcriptional regulators of the corresponding parental genes from which they originate. First, pseudogene genomic sequences can encode siRNAs. Second, pseudogene transcripts can act as indirect post-transcriptional regulators decoying ncRNA, in particular miRNAs that target the parental gene. This has been demonstrated for PTEN and KRAS, two genes involved in tumorigenesis. The role of pseudogenes in disease has not been proven and seems to be the next research landmark. In this review, we chronicle the events following the initial discovery of the ‘useless’ pseudogene to its breakthrough as a functional molecule with hitherto unbeknownst potential to influence human disease.
► We describe the evolution of research on the function of pseudogenes. ► We review the evidence of siRNA expression from pseudogenes. ► Transcripts from pseudogenes have also been found to act as a decoy of miRNAs. ► Finally, we discuss the role of pseudogenes in disease.