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

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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.

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Abbreviations

EST :

Expressed sequence tag

RNP :

Ribonucleoprotein

UTR :

Untranslated region

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Acknowledgements

We thank Dr. Masami Muramatsu, Dr. Munehisa Ueno, Dr. Nobuhiro Deguchi, and Dr. Yoshihiko Funae for generous support. We also thank to Tomohito Itoh, Takumi Matsumoto, Shinji Sasaki, Michiyo Ishida, and Yuzuru Yamauchi for technical support.

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Authors and Affiliations

  1. Department of Genetic Disease Research, Osaka City University Graduate School of Medicine, Asahi-machi 1-4-3 Abeno, 545-8585, Osaka, Japan

    Yoshihisa Yano & Shinji Hirotsune

  2. Institute for Advanced Biosciences, Keio University, Baba-cho 14-1 Tsuruoka, 997-0035, Yamagata, Japan

    Rintaro Saito & Masaru Tomita

  3. Department of Chemical Biology, Osaka City University Graduate School of Medicine, Asahi-machi 1-4-3 Abeno, 545-8585, Osaka, Japan

    Noriyuki Yoshida

  4. Experimental Animal Division, Department of Biological Systems, BioResource Center, RIKEN Tsukuba Institute, 3-1-1 Koyadai, Tsukuba, 305-0074, Ibaraki, Japan

    Atsushi Yoshiki

  5. Departments of Pediatrics and Medicine, UCSD Cancer Center, San Diego School of Medicine, University of California, 9500 Gilman Drive, La Jolla, CA, 92093-0627, USA

    Anthony Wynshaw-Boris

Authors
  1. Yoshihisa Yano
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  2. Rintaro Saito
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  3. Noriyuki Yoshida
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  4. Atsushi Yoshiki
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  5. Anthony Wynshaw-Boris
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  6. Masaru Tomita
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  7. Shinji Hirotsune
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Correspondence to Shinji Hirotsune.

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Y. Yano and R. Saito contributed equally to this work

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Yano, Y., Saito, R., Yoshida, N. et al. A new role for expressed pseudogenes as ncRNA: regulation of mRNA stability of its homologous coding gene. J Mol Med 82, 414–422 (2004). https://doi.org/10.1007/s00109-004-0550-3

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