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

Shinji Hirotsune (), Noriyuki Yoshida, Amy Chen, Lisa Garrett, Fumihiro Sugiyama, Satoru Takahashi, Ken-ichi Yagami, Anthony Wynshaw-Boris and Atsushi Yoshiki
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Shinji Hirotsune: Research Center for Genomic Medicine
Noriyuki Yoshida: Research Center for Genomic Medicine
Amy Chen: National Human Genome Research Institute, NIH
Lisa Garrett: National Human Genome Research Institute, NIH
Fumihiro Sugiyama: University of Tsukuba
Satoru Takahashi: University of Tsukuba
Ken-ichi Yagami: University of Tsukuba
Anthony Wynshaw-Boris: National Human Genome Research Institute, NIH
Atsushi Yoshiki: RIKEN Tsukuba Institute

Nature, 2003, vol. 423, issue 6935, 91-96

Abstract: Abstract A pseudogene is a gene copy that does not produce a functional, full-length protein1. The human genome is estimated to contain up to 20,000 pseudogenes2,3. 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 vicinity of the expressing pseudogene of Makorin1, called Makorin1-p1. This insertion reduced transcription of Makorin1-p1, resulting in destabilization of Makorin1 mRNA in trans by way of a cis-acting RNA decay element within the 5′ region of Makorin1 that is homologous between Makorin1 and Makorin1-p1. Either Makorin1 or Makorin1-p1 transgenes could rescue these phenotypes. Our findings demonstrate a specific regulatory role of an expressed pseudogene, and point to the functional significance of non-coding RNAs.

Date: 2003
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DOI: 10.1038/nature01535

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