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Not So Pseudo Anymore: Pseudogenes As Therapeutic Targets

Overview
Specialties Genetics
Pharmacology
Date 2013 Nov 28
PMID 24279857
Citations 23
Authors
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Abstract

Pseudogenes are junk DNA gene remnants generated by inactivating mutations or the loss of regulatory sequences, often following gene duplication or retrotransposition events. These pseudogenes have previously been considered to be molecular fossils derived from once-coding genes. In many cases, pseudogenes confer no observable selective advantage to the host organism and may be on a path towards removal from the genome. However, pseudogenes can also serve as raw material for the exaptation of novel functions, particularly in relation to the regulation of gene expression. Many pseudogenes are resurrected as noncoding RNA genes, which function in RNA-based gene regulatory circuits. As such, functional pseudogenes might simply be considered as 'genes'. Here, we discuss the role of these pseudogene-derived RNAs as regulators of gene expression in the context of human disease. In particular, we consider the manipulation of pseudogene transcripts through the use of antisense oligonucleotides, siRNAs, aptamers or classical gene therapy approaches as novel pharmacological strategies.

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References
1.
Kleene K, Mulligan E, Steiger D, Donohue K, Mastrangelo M . The mouse gene encoding the testis-specific isoform of Poly(A) binding protein (Pabp2) is an expressed retroposon: intimations that gene expression in spermatogenic cells facilitates the creation of new genes. J Mol Evol. 1998; 47(3):275-81. DOI: 10.1007/pl00006385. View

2.
Franco-Zorrilla J, Valli A, Todesco M, Mateos I, Puga M, Rubio-Somoza I . Target mimicry provides a new mechanism for regulation of microRNA activity. Nat Genet. 2007; 39(8):1033-7. DOI: 10.1038/ng2079. View

3.
Britten R, Davidson E . Repetitive and non-repetitive DNA sequences and a speculation on the origins of evolutionary novelty. Q Rev Biol. 1971; 46(2):111-38. DOI: 10.1086/406830. View

4.
Zou M, Baitei E, Alzahrani A, Al-Mohanna F, Farid N, Meyer B . Oncogenic activation of MAP kinase by BRAF pseudogene in thyroid tumors. Neoplasia. 2008; 11(1):57-65. PMC: 2606119. DOI: 10.1593/neo.81044. View

5.
Han Y, Ma S, Yourek G, Park Y, Garcia J . A transcribed pseudogene of MYLK promotes cell proliferation. FASEB J. 2011; 25(7):2305-12. PMC: 6137860. DOI: 10.1096/fj.10-177808. View