An expressed pseudogene regulates the messenger-RNA stability of its homologous coding gene

@article{Hirotsune2003AnEP,
  title={An expressed pseudogene regulates the messenger-RNA stability of its homologous coding gene},
  author={Shinji Hirotsune and Noriyuki Yoshida and Amy Chen and Lisa J. Garrett and Fumihiro Sugiyama and Satoru Takahashi and Ken‐ichi Yagami and Anthony Wynshaw-Boris and Atsushi Yoshiki},
  journal={Nature},
  year={2003},
  volume={423},
  pages={91-96}
}
A pseudogene is a gene copy that does not produce a functional, full-length protein. The human genome is estimated to contain up to 20,000 pseudogenes. Although much effort has been devoted to understanding the function of pseudogenes, their biological roles remain largely unknown. Here we report the role of an expressed pseudogene—regulation of messenger-RNA stability—in a transgene-insertion mouse mutant exhibiting polycystic kidneys and bone deformity. The transgene was integrated into the… 

A new role for expressed pseudogenes as ncRNA: regulation of mRNA stability of its homologous coding gene

A mutant mouse generated in a course of making a transgenic line that exhibited interesting heterozygote phenotypes provided a clue to uncover a unique role of expressed pseudogenes, demonstrating a novel and specific regulatory role of an expressed pseudogene as well as functional significance for noncoding RNAs.

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The transcribed processed pseudogene (TPΨg), which is disabled but nonetheless transcribed, is identified and is unlike other PΨgs and processed genes in the following ways: (i) they do not show a significant tendency to either deposit on or originate from the X chromosome; (ii) only 5% of human TPΩgs have potential orthologs in mouse; this latter finding indicates that the vast majority of TPάgs is lineage specific.

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The ways in which Pseudogenes exert their effect on coding genes are described and the role of pseudogenes in the increasingly complex web of noncoding RNA that contributes to normal cellular regulation is explored.

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This chapter defines pseudogenes, describes the evidence that they are transcribed into non-coding RNAs and outlines the mechanisms by which they are able to influence the machinery of the eukaryotic cell.

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A large class of non-standard but potentially functional transcripts that are likely to encode genetic information and effect biological processes in novel ways are surveyed, implying fundamental limits to the goal of annotating all functional elements at the genome sequence level.

Assessing the genomic evidence for conserved transcribed pseudogenes under selection

Through evolutionary analysis, the genomic evidence for functional human transcribed pseudogenes of potential functional importance is assessed, and 68 human TPAs that are syntenically conserved in at least two other mammals are identified.

The putatively functional Mkrn1-p1 pseudogene is neither expressed nor imprinted, nor does it regulate its source gene in trans

It is shown that 5’ Mkrn1-p1 is fully methylated on both alleles, a pattern indicative of silenced chromatin, and that Mkrn2- p1 is not transcribed and therefore cannot stabilize Mkrn 1 transcripts in trans, which invalidates the data upon which the pseudogene trans-regulation model is based and strongly supports the view that mammalian pseudogenes are evolutionary relics.

Nonneutral evolution of the transcribed pseudogene Makorin1-p1 in mice.

It is shown that Makorin1-p1 originated after the separation of Mus and Rattus but before the divergence of M. musculus and M. pahari, illustrating the potential of using evolutionary analysis to identify pseudogenes from genome sequences.
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