Abstract
BackgroundSMRT and NCoR are corepressor paralogs that help mediate transcriptional repression by a variety of transcription factors, including the nuclear hormone receptors. The functions of both corepressors are extensively diversified in mice by alternative mRNA splicing, generating a series of protein variants that differ in different tissues and that exert different, even diametrically opposite, biochemical and biological effects from one another.ResultsWe report here that the alternative splicing previously reported for SMRT appears to be a relatively recent evolutionary phenomenon, with only one of these previously identified sites utilized in a teleost fish and a limited additional number of the additional known sites utilized in a bird, reptile, and marsupial. In contrast, extensive SMRT alternative splicing at these sites was detected among the placental mammals. The alternative splicing of NCoR previously identified in mice (and shown to regulate lipid and carbohydrate metabolism) is likely to have arisen separately and after that of SMRT, and includes an example of convergent evolution.ConclusionsWe propose that the functions of both SMRT and NCoR have been diversified by alternative splicing during evolution to allow customization for different purposes in different tissues and different species.Electronic supplementary materialThe online version of this article (doi:10.1186/s12862-016-0781-2) contains supplementary material, which is available to authorized users.
Highlights
SMRT and NCoR are corepressor paralogs that help mediate transcriptional repression by a variety of transcription factors, including the nuclear hormone receptors
We began with liver as a model organ; the livers of mice and Xenopus express a representation of all the alternative spliced variants of both SMRT and NCoR reported for these species [21]
The SMRT 40b + and 40b- splice variants display very different preferences for different transcription factors, most clearly seen as a highly divergent ability to interact with the thyroid hormone receptor (TR) and with the peroxisome-proliferator activating receptor (PPAR)-γ, both of which play important roles in overall metabolism [22, 23]
Summary
SMRT and NCoR are corepressor paralogs that help mediate transcriptional repression by a variety of transcription factors, including the nuclear hormone receptors. The functions of both corepressors are extensively diversified in mice by alternative mRNA splicing, generating a series of protein variants that differ in different tissues and that exert different, even diametrically opposite, biochemical and biological effects from one another. SMRT and NCoR are important corepressors for the nuclear hormone receptors and for many additional, non-receptor transcription factors [3, 9,10,11,12,13,14,15].
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