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

Speaker：葉 承 昀

Commentator：劉 校 生 教授

Time：Dec. 24, 2003; 15:00~16:00

Place：601

Abstract：

The “pseudogene” was originally detected in the genome Xenopus laevi¹, which was defined as a gene that does not have function in the cell.  In this paper, the authors created a transgenic mouse carrying the Drosophila sex-lethal gene.  This transgenic mouse exhibited the phenotype with polycystic kidney and bone deformity².  Unexpectedly, the authors found that the transgene was inserted in Makorin1-p1, a pseudogene.  Makorin1-p1 is 700 bp long and has a 5’ end sequence region overlapping with the gene Makorin1. Makorin1 is the functional copy of the pseudogeneMakorin1-p1, which with a ring-finger motif belongs to the ubiquitinase E3 family³. When the pseudogene Makorin1-p1 was knocked out in the transgenic mouse, Makorin1 mRNA was degraded more easily due to the sequence of its 5’ region.  The authors proposed that there is a RNA-destabilizing factor which can bind to the 5’ region of Makorin1 and Makorin1-p1 genes.  Makorin1-p1could disperse the factor to bind Makorin1, therefore decreased Makorin1 degradation.  The authors further injected either Makorin1 or Makorin1-p1 plasmid into the transgenic mouse to overexpress these genes, and the aberrant phenotype of the transgenic mouse was successfully rescued.  These findings demonstrate that the pseudogene is able to play a regulatory role, and points to the functional significance of non-coding RNAs in the cell.

References：

1.         Jacq, C., Miller, J. R. & Brownlee, G. G. A pseudogene structure in 5S DNA of Xenopus laevis. Cell 12, 109-20 (1977).

2.         Hirotsune, S. et al. An expressed pseudogene regulates the messenger-RNA stability of its homologous coding gene. Nature 423, 91-6 (2003).

3.         Yoshida, N. et al. Identification of a new target molecule for a cascade therapy of polycystic kidney. Hum Cell 16, 65-72 (2003).