title: A new role for expressed pseudogenes as ncRNA: regulation of mRNA stability of its homologous coding gene.
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.
authors.affiliation: Department of Genetic Disease Research, Osaka City University Graduate School of Medicine, Asahi-machi 1-4-3 Abeno, 545-8585 Osaka, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Yano
authors.forename: Rintaro
authors.initials: R
authors.lastname: Saito
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Yoshida
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yoshiki
authors.forename: Anthony
authors.initials: A
authors.lastname: Wynshaw-Boris
authors.forename: Masaru
authors.initials: M
authors.lastname: Tomita
authors.forename: Shinji
authors.initials: S
authors.lastname: Hirotsune
mesh_terms: D000818:Animals; D004622:Embryo, Mammalian / Q000002:abnormalities; D047108:Embryonic Development / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins; D011544:Pseudogenes / Q000235:genetics*; D020871:RNA Stability / Q000235:genetics*; D012261:Ribonucleoproteins / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid
chemical_list: C410808:Makorin ring finger protein 1; D009419:Nerve Tissue Proteins; D012261:Ribonucleoproteins