A new role for expressed pseudogenes as ncRNA: Regulation of mRNA stability of is homologous coding gene

Yoshihisa Yano, Rintaro Saito, Noriyuki Yoshida, Atsushi Yoshiki, Anthony Wynshaw-Boris, Masaru Tomita, Shinji Hirotsune

Research output: Contribution to journalReview articlepeer-review

59 Citations (Scopus)

Abstract

We have earlier generated a mutant mouse in a course of making a transgenic line that exhibited interesting heterozygote phenotypes, which exhibited failure to thrive, severe bone deformities, and polycystic kidneys. This mutant mouse provided a clue to uncover a unique role of expressed pseudogenes. In this mutant the transgene was integrated into the vicinity of the expressing pseudogene of Makorin1 called Makorin1-p1. This insertion reduced transcription of the Makorin1-p1, resulting in destabilization of the Makorin1 mRNA in trans via a cis-acting RNA decay element within the 5′ region of Makorin1 that is homologous between Makorin1 and Makorin1-p1. These findings demonstrate a novel and specific regulatory role of an expressed pseudogene as well as functional significance for noncoding RNAs. Next, we developed an original algorithm to determine how many pseudogenes are expressed. Based on our examination 2-3% of human processed pseudogenes are expressed using the most strict criteria. Interestingly, the mouse has a much smaller proportion of expressed pseudogenes (0.5-1%). Pseudogenes are functionally less constrained, and have accumulated more mutations than translated genes. If they have some functions in gene regulation, this property would allow more rapid functional diversification than protein-coding genes. In addition, some genetic phenomena that exhibit incomplete penetrance might be attributed to "mutation" or "variation" of pseudogenes.

Original languageEnglish
Pages (from-to)414-422
Number of pages9
JournalJournal of Molecular Medicine
Volume82
Issue number7
DOIs
Publication statusPublished - 2004 Jul

Keywords

  • Evolution
  • Junk DNA
  • Pseudogene
  • mRNA decay
  • ncRNA

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Genetics(clinical)

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