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Methods in Molecular Biology (Clifton,... 2014Pseudogenes were once considered genomic fossils, but recent studies indicate that they may function as gene regulators through the generation of endogenous small... (Review)
Review
Pseudogenes were once considered genomic fossils, but recent studies indicate that they may function as gene regulators through the generation of endogenous small interfering RNAs (esiRNAs), antisense RNAs, and decoys for microRNAs. In this review, we summarize pseudogene study methods, emphasizing relevant publicly available resources, and we describe a systematic pipeline to identify pseudogene-derived esiRNAs and their targets, which can lead to a deeper understanding of pseudogene function.
Topics: Animals; Computational Biology; Databases, Nucleic Acid; Genome-Wide Association Study; Humans; Molecular Sequence Annotation; Pseudogenes; RNA, Small Interfering; Web Browser
PubMed: 24823781
DOI: 10.1007/978-1-4939-0835-6_15 -
Methods in Molecular Biology (Clifton,... 2021The number of complete genome sequences explodes more and more with each passing year. Thus, methods for genome annotation need to be honed constantly to handle the... (Review)
Review
The number of complete genome sequences explodes more and more with each passing year. Thus, methods for genome annotation need to be honed constantly to handle the deluge of information. Annotation of pseudogenes (i.e., gene copies that appear not to make a functional protein) in genomes is a persistent problem; here, we overview pseudogene annotation methods that are based on the detection of sequence homology in genomic DNA.
Topics: Animals; Computational Biology; Genomics; Humans; Molecular Sequence Annotation; Pseudogenes; Sequence Alignment; Sequence Analysis, DNA; Sequence Homology; Software
PubMed: 34165707
DOI: 10.1007/978-1-0716-1503-4_3 -
Tumour Biology : the Journal of the... Feb 2016Over the past decade, the importance of non-protein-coding functional elements in the human genome has emerged from the water and been identified as a key revelation in... (Review)
Review
Over the past decade, the importance of non-protein-coding functional elements in the human genome has emerged from the water and been identified as a key revelation in post-genomic biology. Since the completion of the ENCODE (Encyclopedia of DNA Elements) and FANTOM (Functional Annotation of Mammals) project, tens of thousands of pseudogenes as well as numerous long non-coding RNA (lncRNA) genes were identified. However, while pseudogenes were initially regarded as non-functional relics littering the human genome during evolution, recent studies have revealed that they play critical roles at multiple levels in diverse physiological and pathological processes, especially in cancer through parental-gene-dependent or parental-gene-independent regulation. Herein, we review the current knowledge of pseudogenes and synthesize the nascent evidence for functional properties and regulatory modalities exerted by pseudogene-transcribed RNAs in human cancers and prospect the potential as molecular signatures in cancer reclassification and tailored therapy.
Topics: Animals; Gene Expression Regulation, Neoplastic; Humans; Neoplasms; Pseudogenes; RNA
PubMed: 26662308
DOI: 10.1007/s13277-015-4482-z -
Journal of Medical Genetics Jan 2015Pseudogenes were initially regarded as non-functional genomic fossils resulted from inactivating gene mutations during evolution. However, later studies revealed that... (Review)
Review
Pseudogenes were initially regarded as non-functional genomic fossils resulted from inactivating gene mutations during evolution. However, later studies revealed that they play a plethora of roles at multiple levels (DNA, RNA and/or protein) in diverse physiological and pathological processes, especially in cancer, both parental-gene-dependently and parental-gene-independently. Pseudogenes can interact with parental genes or other gene loci, leading to alteration in their sequences and/or transcriptional activities. Pseudogene-derived RNAs play multifaceted roles in post-transcriptional regulation as antisense RNAs, endogenous small-interference RNAs, competing endogenous RNAs and so on. Pseudogenic proteins can mirror, mimic or interfere with the functions of their parental counterparts. Herein, we discuss the general aspects (origination, classification, identification) of pseudogenes, focus on their multiple functions in cancer pathogenesis and prospect the potentials they hold as molecular signatures assisting in cancer reclassification and tailored therapy.
Topics: DNA, Intergenic; Humans; Models, Genetic; Mutation; Neoplasms; Pseudogenes; RNA, Antisense
PubMed: 25391452
DOI: 10.1136/jmedgenet-2014-102785 -
Current Topics in Microbiology and... 2016Pseudogenes have for long been considered as non-functional relics littering the human genome. Only now, it is becoming apparent that many pseudogenes are transcribed... (Review)
Review
Pseudogenes have for long been considered as non-functional relics littering the human genome. Only now, it is becoming apparent that many pseudogenes are transcribed into long noncoding RNAs, some with proven biological functions. Here, we review the current knowledge of pseudogenes and their widespread functional properties with an emphasis on pseudogenes that have been functionally investigated in greater detail. Pseudogenes are emerging as a novel class of long noncoding RNAs functioning, for example, through microRNA sponging and chromatin remodeling. The examples discussed herein underline that pseudogene-encoded RNAs are important regulatory molecules involved in diseases such as cancer.
Topics: HMGA1a Protein; Humans; Neoplasms; Octamer Transcription Factor-3; PTEN Phosphohydrolase; Pseudogenes; RNA, Long Noncoding
PubMed: 25982975
DOI: 10.1007/82_2015_442 -
Nippon Ganka Gakkai Zasshi Dec 2009
Review
Topics: DNA; DNA, Intergenic; Genetic Diseases, Inborn; Humans; Pseudogenes; RNA; RNA, Untranslated
PubMed: 20058672
DOI: No ID Found -
Cell Cycle (Georgetown, Tex.) 2014Two pseudogenes for HMGA1, whose overexpression has a critical role in cancer progression, have been identified. They act as decoy for miRNAs that are able to target the... (Review)
Review
Two pseudogenes for HMGA1, whose overexpression has a critical role in cancer progression, have been identified. They act as decoy for miRNAs that are able to target the HMGA1 gene then enhancing cell proliferation and migration. Moreover, these pseudogenes contain sequences that are potential target sites for cancer-related miRNAs. Interestingly, HMGA1 pseudogenes are highly expressed in human anaplastic thyroid carcinomas, that is one of the most aggressive tumor in mankind, but almost undetectable in well differentiated thyroid carcinomas.
Topics: Animals; Cell Proliferation; Disease Progression; Gene Expression Regulation, Neoplastic; HMGA Proteins; Humans; MicroRNAs; Neoplasms; Pseudogenes
PubMed: 25483074
DOI: 10.4161/15384101.2014.974440 -
Methods in Molecular Biology (Clifton,... 2014The study of pseudogenes, originally dismissed as genomic relics of evolutionary selection, has seen a resurgence in scientific literature, in addition to being a... (Review)
Review
The study of pseudogenes, originally dismissed as genomic relics of evolutionary selection, has seen a resurgence in scientific literature, in addition to being a peculiar topic of discussion in theological debates. For a long time, pseudogenes have been touted as a beacon of natural selection and a definitive proof of evolution due to the slow mutation rate that differentiated them from their parental genes and ultimately caused their genetic demise as functional genes. It now seems that "creationists" have co-opted some recent reports identifying unheralded biological functions to pseudogens and other noncoding RNAs as evidence to undermine the existence of evolution and supporting intelligent design. This issue of Methods in Molecular Biology focused on pseudogenes will certainly not end, nor enter this debate; however, scientists who are also genomics and pseudogene enthusiasts will certainly appreciate that many scientists are thinking about these particular genetic elements in new and interesting ways. With this new interest in a biological significance and "non-junk" role for pseudogenes and other noncoding RNAs, new methods and approaches are being developed to unlock the mystery of these ancient artifacts we know as pseudogenes. In this brief introductory chapter we highlight the renewed interest in pseudogenes and review a rationale for intensification of pseudogene-related research.
Topics: Epistasis, Genetic; Gene Expression Regulation; Humans; Pseudogenes; Transcription, Genetic
PubMed: 24823767
DOI: 10.1007/978-1-4939-0835-6_1 -
Nature Communications Mar 2020Pseudogenes are mutated copies of protein-coding genes that cannot be translated into proteins, but a small subset of pseudogenes has been detected at the protein level....
Pseudogenes are mutated copies of protein-coding genes that cannot be translated into proteins, but a small subset of pseudogenes has been detected at the protein level. Although ubiquitin pseudogenes represent one of the most abundant pseudogene families in many organisms, little is known about their expression and signaling potential. By re-analyzing public RNA-sequencing and proteomics datasets, we here provide evidence for the expression of several ubiquitin pseudogenes including UBB pseudogene 4 (UBBP4), which encodes Ub (Q2K, K33E, Q49K, N60S). The functional consequences of Ub conjugation appear to differ from canonical ubiquitylation. Quantitative proteomics shows that Ub modifies specific proteins including lamins. Knockout of UBBP4 results in slower cell division, and accumulation of lamin A within the nucleolus. Our work suggests that a subset of proteins reported as ubiquitin targets may instead be modified by ubiquitin variants that are the products of wrongly annotated pseudogenes and induce different functional effects.
Topics: CRISPR-Cas Systems; Cell Division; Cell Nucleus; Cloning, Molecular; Datasets as Topic; Gene Knockout Techniques; HEK293 Cells; HeLa Cells; Humans; Lamin Type A; Proteomics; Pseudogenes; RNA-Seq; Ubiquitin; Ubiquitination
PubMed: 32161257
DOI: 10.1038/s41467-020-15090-6 -
The International Journal of... Sep 2014A paradigm shift is sweeping modern day molecular biology following the realisation that large amounts of "junk" DNA", thought initially to be evolutionary remnants, may... (Review)
Review
A paradigm shift is sweeping modern day molecular biology following the realisation that large amounts of "junk" DNA", thought initially to be evolutionary remnants, may actually be functional. Several recent studies support a functional role for pseudogene-expressed non-coding RNAs in regulating their protein-coding counterparts. Several hundreds of pseudogenes have been reported as transcribed into RNA in a large variety of tissues and tumours. Most studies have focused on pseudogenes expressed in the sense direction, but some reports suggest that pseudogenes can also be transcribed as antisense RNAs (asRNAs). A few examples of key regulatory genes, such as PTEN and OCT4, have in fact been reported to be under the regulation of pseudogene-expressed asRNAs. Here, we review what are known about pseudogene expressed non-coding RNA mediated gene regulation and their roles in the control of epigenetic states. This article is part of a Directed Issue entitled: The Non-coding RNA Revolution.
Topics: Animals; Epigenomics; Gene Expression Regulation; Humans; Pseudogenes; RNA, Antisense; RNA, Long Noncoding; Transcription, Genetic
PubMed: 24842102
DOI: 10.1016/j.biocel.2014.05.008