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

Abstract

A pseudogene is a gene copy that does not produce a functional, full-length protein. The human genome is estimated to contain up to 20,000 pseudogenes. 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.

Lamr1 functional retroposon causes right ventricular dysplasia in mice

“…It has also been suggested that the Lamr1 gene family in mammals, with the exception of the functional locus, is comprised entirely of retrotransposons or processed pseudogenes. Most processed retroposons are not expressed and have no functional activity, but several active retroposons or pseudogenes have been identified [29][30][31][32] . We show that the active retroposon may cause the pathological condition of ARVD.…”

Expanding the ‘central dogma’: the regulatory role of nonprotein coding genes and implications for the genetic liability to schizophrenia

“…The pseudogene was discovered fortuitously while conducting a study which involved inserting a Drosophila gene Sex-Lethal randomly into the mouse genome. 27 This gene insertion was fatal for one line of mice. Surprisingly, the Sex-Lethal gene had been inserted in the middle of a pseudogene, Makorin1p, located on murine chromosome 5.…”

An analysis of effects of heterozygosity in dairy cattle for bovine tuberculosis resistance

“…In Ensembl, blasting the sequence of peroxiredoxin‐6‐like pseudogene against that of the peroxiredoxin‐6 gene (BTA16) confirmed that peroxiredoxin‐6 is the parental gene of peroxiredoxin‐6‐like pseudogene and that the latter is likely to be a processed pseudogene, as the parental gene resides on a different chromosome (Vanin 1985; Hirotsune et al . 2003; Kandouz et al . 2004; Bischof et al .…”