Abstract
Pseudogenes have been known as non-functional molecular relics developed from inactivated genomic mutations while evolution. However, they have a various function at distinct molecular stages (DNA, RNA and protein) in different biological events including in cancer and associated with parental-gene-dependently and parental-gene independently. The interactions of pseudogenes with ancestor genes or other genes alter in their sequences and transcriptional processes. Pseudogene of RNA sequences have multiple functions in post-transcriptional activities as antisense RNAs, endogenous small-interference RNAs, and competing endogenous RNAs. Moreover, it also plays vital roles in controlling of its parent genes and other pseudogenes transcribing into RNA. Pseudogene transcripts make small interfering RNA or decline cellular miRNA level. The current review focuses on pseudogene functional signature in human genome by regulating the gene expression.
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References
Bischof JM, Chiang AP, Scheetz TE et al (2006) Genome-wide identification of pseudogenes capable of disease-causing gene conversion. Hum Mutat. https://doi.org/10.1002/humu.20335
Bossi L, Figueroa-Bossi N (2016) Competing endogenous RNAs: a target-centric view of small RNA regulation in bacteria. Nat Rev Microbiol 14:775–784
Cantz T, Key G, Bleidiβel M et al (2007) Absence of OCT4 expression in somatic tumor cell lines. Stem Cells. https://doi.org/10.1634/stemcells.2007-0657
Carninci P (2008) Non-coding RNA transcription: Turning on neighbours. Nat Cell Biol. https://doi.org/10.1038/ncb0908-1023
Chan WL, Chang JG (2014) Pseudogene-derived endogenous sirnas and their function. Methods Mol Biol. https://doi.org/10.1007/978-1-4939-0835-6_15
Chu C, Qu K, Zhong FL et al (2011) Genomic maps of long noncoding RNA occupancy reveal principles of RNA-chromatin interactions. Mol Cell. https://doi.org/10.1016/j.molcel.2011.08.027
Comings DE (1972) The structure and function of chromatin. Adv Hum Genet 3:237–431
Core LJ, Waterfall JJ, Lis JT (2008) Nascent RNA sequencing reveals widespread pausing and divergent initiation at human promoters. Science 5(80):5. https://doi.org/10.1126/science.1162228
Davis AP, Benninghoff AD, Thomas AJ et al (2015) DNA methylation of the LIN28 pseudogene family. BMC Genom. https://doi.org/10.1186/s12864-015-1487-3
Elliott KT, Cuff LE, Neidle EL (2013) Copy number change: evolving views on gene amplification. Future Microbiol 8:887–899
Gong C, Maquat LE (2011) LncRNAs transactivate STAU1-mediated mRNA decay by duplexing with 39 UTRs via Alu eleme. Nature. https://doi.org/10.1038/nature09701
Guo X, Deng L, Deng K et al (2016) Pseudogene PTENP1 suppresses gastric cancer progression by modulating PTEN. Anticancer Agents Med Chem. https://doi.org/10.2174/1871520615666150507121407
Gutschner T, Diederichs S (2012) The hallmarks of cancer: a long non-coding RNA point of view. RNA Biol 9:703–719
Hafner M, Landthaler M, Burger L et al (2010) Transcriptome-wide Identification of RNA-binding protein and MicroRNA target sites by PAR-CLIP. Cell. https://doi.org/10.1016/j.cell.2010.03.009
Han YJ, Ma SF, Yourek G et al (2011) A transcribed pseudogene of MYLK promotes cell proliferation. FASEB J. https://doi.org/10.1096/fj.10-177808
Hawkins PG, Morris KV (2010) Transcriptional regulation of Oct4 by a long non-coding RNA antisense to Oct4-pseudogene 5. Transcription. https://doi.org/10.4161/trns.1.3.13332
Stedman HH, Kozyak BW, Nelson A et al (2004) Myosin gene mutation correlates with anatomical changes in the human lineage. Nature 428:415–418
Hung T, Wang Y, Lin MF et al (2011) Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters. Nat Genet 43:621–629
Hwang SL, Chang JH, Cheng CY et al (2005) The expression of rac1 pseudogene in human tissues and in human brain tumors. Eur Surg Res. https://doi.org/10.1159/000084540
Ishiguro T, Sato A, Ohata H et al (2012) Differential expression of nanog1 and nanogp8 in colon cancer cells. Biochem Biophys Res Commun. https://doi.org/10.1016/j.bbrc.2011.10.123
Jacq C, Miller JR, Brownlee GG (1977) A pseudogene structure in 5S DNA of Xenopus laevis. Cell. https://doi.org/10.1016/0092-8674(77)90189-1
Jeter CR, Badeaux M, Choy G, Chandra D, Patrawala L et al (2009) Functional evidence that the self-renewal gene NANOG regulates human tumor development. Stem Cells 27:993–1005. https://doi.org/10.1002/stem.29
Johnsson P, Ackley A, Vidarsdottir L et al (2013) A pseudogene long-noncoding-RNA network regulates PTEN transcription and translation in human cells. Nat Struct Mol Biol. https://doi.org/10.1038/nsmb.2516
Kalyana-Sundaram S, Kumar-Sinha C, Shankar S et al (2012) Expressed pseudogenes in the transcriptional landscape of human cancers. Cell. https://doi.org/10.1016/j.cell.2012.04.041
Karreth FA, Reschke M, Ruocco A et al (2015) The BRAF pseudogene functions as a competitive endogenous RNA and induces lymphoma in vivo. Cell. https://doi.org/10.1016/j.cell.2015.02.043
Karro JE, Yan Y, Zheng D et al (2007) Pseudogene.org: a comprehensive database and comparison platform for pseudogene annotation. Nucleic Acids Res. https://doi.org/10.1093/nar/gkl851
Khachane AN, Harrison PM (2009) Assessing the genomic evidence for conserved transcribed pseudogenes under selection. BMC Genom. https://doi.org/10.1186/1471-2164-10-435
Levine M, Tjian R (2003) Transcription regulation and animal diversity. Nature 424:147–151
Ling H, Vincent K, Pichler M et al (2015) Junk DNA and the long non-coding RNA twist in cancer genetics. Oncogene 34:5003–5011
Maranda V, Sunstrum FG, Drouin G (2019) Both male and female gamete generating cells produce processed pseudogenes in the human genome. Gene. https://doi.org/10.1016/j.gene.2018.10.061
Martin L, Meier M, Lyons SM et al (2012) Systematic reconstruction of RNA functional motifs with high-throughput microfluidics. Nat Methods. https://doi.org/10.1038/nmeth.2225
Mathews CK (2017) Junk DNA: a journey through the dark matter of the genome. FASEB J. https://doi.org/10.1096/fj.201700951
Nakano M, Fukushima Y, Yokota SI et al (2015) CYP2A7 pseudogene transcript affects CYP2A6 expression in human liver by acting as a decoy for MIR-126. Drug Metab Dispos. https://doi.org/10.1124/dmd.115.063255
Paige JS, Wu KY, Jaffrey SR (2011) RNA mimics of green fluorescent protein. Science. https://doi.org/10.1126/science.1207339
Pink RC, Wicks K, Caley DP, Punch EK, Jacobs LCD (2011) Pseudogenes: pseudo-functional or key regulators in health and disease? RNA 17:792–798
Poliseno L (2012) Pseudogenes: Newly discovered players in human cancer. Sci Signal 5:1–14
Poliseno L, Marranci A, Pandolfi PP (2015) Pseudogenes in human cancer. Front Med 2:68. https://doi.org/10.3389/fmed.2015.00068
Poliseno L, Pandolfi PP (2015) PTEN ceRNA networks in human cancer. Methods 77–78:41–50
Poliseno L, Salmena L, Zhang J et al (2010) A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature. https://doi.org/10.1038/nature09144
Porter KA, Duffy EB, Nyland P et al (2014) The CLRX.1/NOD24 (NLRP2P) pseudogene codes a functional negative regulator of NFkappaB, pyrin-only protein 4. Genes Immun 15:392–403
Saleh M, Vaillancourt JP, Graham RK et al (2004) Differential modulation of endotoxin responsiveness by human caspase-12 polymorphisms. Nature. https://doi.org/10.1038/nature02451
Salmena L (2014) Pseudogene redux with new biological significance. Methods Mol Biol. https://doi.org/10.1007/978-1-4939-0835-6_1
Sasidharan R, Gerstein M (2008) Genomics: protein fossils live on as RNA. Nature 453:729–731
Scarola M, Comisso E, Pascolo R et al (2015) Epigenetic silencing of Oct4 by a complex containing SUV39H1 and Oct4 pseudogene lncRNA. Nat Commun. https://doi.org/10.1038/ncomms8631
Schmitz KM, Mayer C, Postepska A, Grummt I (2010) Interaction of noncoding RNA with the rDNA promoter mediates recruitment of DNMT3b and silencing of rRNA genes. Genes Dev. https://doi.org/10.1101/gad.590910
Seila AC, Calabrese JM, Levine SS et al (2008) Divergent transcription from active promoters. Science. https://doi.org/10.1126/science.1162253
Skaletsky H, Kuroda-Kawaguchl T, Minx PJ et al (2003) The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes. Nature. https://doi.org/10.1038/nature01722
Takahashi K, Tanabe K, Ohnuki M et al (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. https://doi.org/10.1016/j.cell.2007.11.019
Tay Y, Rinn J, Pandolfi PP (2014) The multilayered complexity of ceRNA crosstalk and competition. Nature 505:344–352
Thomson DW, Dinger ME (2016) Endogenous microRNA sponges: evidence and controversy. Nat Rev Genet. https://doi.org/10.1038/nrg.2016.20
Tutar Y (2012) Pseudogenes. Comp Funct Genom 2012:424–526
Veerappa AM, Padakannaya P, Ramachandra NB (2013) Copy number variation-based polymorphism in a new pseudoautosomal region 3 (PAR3) of a human X-chromosome-transposed region (XTR) in the Y chromosome. Funct Integr Genom. https://doi.org/10.1007/s10142-013-0323-6
Wang X, Grus WE, Zhang J (2006) Gene losses during human origins. PLoS Biol. https://doi.org/10.1371/journal.pbio.0040052
Xiao-Jie L, Ai-Mei G, Li-Juan J, Jiang X (2015) Pseudogene in cancer: real functions and promising signature. J Med Genet. https://doi.org/10.1136/jmedgenet-2014-102785
Zhang J, Wang X, Li M et al (2006) NANOGP8 is a retrogene expressed in cancers. FEBS J. https://doi.org/10.1002/qua.20952
Zhang Z, Zheng D (2014) Pseudogene evolution in the human genome. https://doi.org/10.1002/9780470015902.a0020836.pub2
Zhang Z, Zhu Z, Watabe K et al (2013) Negative regulation of lncRNA GAS5 by miR-21. Cell Death Differ. https://doi.org/10.1038/cdd.2013.110
Zheng L, Li X, Gu Y et al (2015) The 3′UTR of the pseudogene CYP4Z2P promotes tumor angiogenesis in breast cancer by acting as a ceRNA for CYP4Z1. Breast Cancer Res Treat. https://doi.org/10.1007/s10549-015-3298-2
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Singh, R.K., Singh, D., Yadava, A. et al. Molecular fossils “pseudogenes” as functional signature in biological system. Genes Genom 42, 619–630 (2020). https://doi.org/10.1007/s13258-020-00935-7
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DOI: https://doi.org/10.1007/s13258-020-00935-7