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An imprinted, mammalian bicistronic transcript encodes two independent proteins.
T A Gray1, S Saitoh, R D Nicholls
1Department of Genetics, Case Western Reserve University School of Medicine and Center for Human Genetics, University Hospitals of Cleveland, OH 44106, USA.
Summary
Polycistronic transcripts, rare in mammals, were found to encode SNURF and SNRPN proteins. This bicistronic transcript is linked to Prader-Willi syndrome and suggests functional operons in mammalian genomes.
Area of Science:
- Genomics
- Molecular Biology
- Evolutionary Biology
Background:
- Polycistronic transcripts are common in prokaryotes but rare in eukaryotes.
- The SNRPN (SmN) mRNA in mammals has been studied, but upstream regions are less understood.
Purpose of the Study:
- To investigate the evolutionary conservation and function of the SNRPN upstream reading frame (SNURF).
- To determine the role of SNURF and SNRPN in the imprinted Prader-Willi syndrome (PWS).
Main Methods:
- Phylogenetic analysis of SNRPN mRNA in five eutherian mammals.
- Analysis of nucleotide substitutions in the SNURF region.
- Examination of SNURF and SNRPN expression and translation in human and mouse tissues and cell lines.
Main Results:
- A highly conserved coding sequence, SNURF, was identified upstream of SNRPN.
- SNURF shows strong evolutionary evidence for protein-coding function, with substitutions at wobble codon positions.
- SNURF and SNRPN are translated from a bicistronic transcript in normal human and mouse tissues, but not in PWS models.
Conclusions:
- SNURF is a protein produced with SmN from a bicistronic transcript, indicating functional operons in mammalian genomes.
- The SNURF-SNRPN locus is paternally expressed and implicated in Prader-Willi syndrome.
- SNURF may have been the original selection for imprinting in the 15q11-q13 region.