Concerted regulation and molecular evolution of the duplicated SNRPB'/B and SNRPN loci

Todd A. Gray, Megan J. Smithwick, Melanie A. Schaldach, Diana L. Martone, Jennifer A. Marshall Graves, John R. McCarrey, Robert D. Nicholls

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

The human small nuclear ribonucleoprotein SNRPB'/B gene is alternatively spliced to produce the SmB or SmB' spliceosomal core proteins. An ancestral duplication gave rise to the closely related SNRPN paralog whose protein product, SmN, replaces SmB'/B in brain. However, the precise evolutionary and functional relationship between these loci has not been clear. Genomic, cDNA and protein analyses presented here in chicken, two marsupials (South American opossum and tammar wallaby), and hedgehog, suggest that the vertebrate ancestral locus produced the SmB' isoform. Interestingly, three eutherians exhibit radically distinct splice choice expression profiles, producing either exclusively SmB in mouse, both SmB and SmB' in human, or exclusively SmB' in hedgehog. The human SNRPB'/B locus is biallelically unmethylated, unlike the imprinted SNRPN locus which is unmethylated only on the expressed paternal allele. Western analysis demonstrates that a compensatory feedback loop dramatically upregulates SmB'/B levels in response to the loss of SmN in Prader-Willi syndrome brain tissue, potentially reducing the phenotypic severity of this syndrome. These findings imply that these two genes encoding small nuclear ribonucleoprotein components are subject to dosage compensation. Therefore, a more global regulatory network may govern the maintenance of stoichiometric levels of spliceosomal components and may constrain their evolution.

Original languageEnglish (US)
Pages (from-to)4577-4584
Number of pages8
JournalNucleic acids research
Volume27
Issue number23
DOIs
StatePublished - Dec 1 1999
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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