RRC ID 2388
Author Hirotsune S, Yoshida N, Chen A, Garrett L, Sugiyama F, Takahashi S, Yagami K, Wynshaw-Boris A, Yoshiki A.
Title An expressed pseudogene regulates the messenger-RNA stability of its homologous coding gene.
Journal Nature
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.
Volume 423(6935)
Pages 91-6
Published 2003-5-1
DOI 10.1038/nature01535
PII nature01535
PMID 12721631
MeSH Alleles Animals Base Sequence Bone and Bones / abnormalities Female Gene Expression Regulation* Genomic Imprinting Genotype Male Mice Mice, Transgenic Molecular Sequence Data Mutagenesis, Insertional Nerve Tissue Proteins Phenotype Polycystic Kidney Diseases / genetics Pseudogenes / genetics* Pseudogenes / physiology* RNA Stability* RNA, Messenger / genetics RNA, Messenger / metabolism* RNA, Untranslated / genetics RNA, Untranslated / physiology Ribonucleoproteins / genetics* Transcription, Genetic / genetics Transgenes / genetics
IF 42.779
Times Cited 306
WOS Category GENETICS & HEREDITY
Resource
Mice RBRC00208