Ternative splicing at these sites was detected among Acetamiprid
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. Conclusions: We 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. Keywords: Corepressor, NCoR, SMRT, mRNA splicing, EvolutionBackground The nuclear hormone receptors are ligand-modulated transcription factors involved in the regulation of many developmental and homeostatic processes (1?). The transcriptional properties of these receptors are mediated through their recruitment and release of auxiliary proteins, denoted corepressors and coactivators [1?]. SMRT and NCoR are important corepressors for the nuclear PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/27919709
hormone receptors and for many additional, non-receptor transcription factors [3, 9?5]. Both SMRT and NCoR function as bridging proteins, possessing both specific domains that recruit them to their transcription factor partners and separate regions that bind additional components PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28024961
of a larger corepressor complex; the complex inhibits transcription by modifying the chromatin template and/or by interfering with components of the transcriptional machinery [3, 16]. SMRT and NCoR are present as two distinct loci in vertebrate genomes. In contrast, only single SMRT/* Correspondence: email@example.com Department of Microbiology and Molecular Genetics, College of Biological Sciences, University of California at Davis, One Shields Avenue, Davis, CA 95616, USANCoR-like loci have been detected in the genomes of other deuterostomes, including the non-vertebrate chordata and echinoderms . This supports the concept that NCoR and SMRT are paralogs that arose from an ancestral gene duplication and divergence. More weakly related loci (e.g., SMRTER and GEI-8) are found in yet more divergent phyla such as the arthropoda and nematoda [18, 19] although these bear only isolated blocks of sequence relatedness and lack many other structural features found in the chordate NCoR/SMRT (such as the "CoRNR box" motifs/Receptor Interaction Domains (RIDs) responsible for the interaction of the vertebrate corepressors with their nuclear receptor partners). Both SMRT and NCoR in mice and humans are expressed by extensive alternative mRNA splicing to yield a series of protein variants that are expressed at different relative abundances in different tissues, possess different RIDS, have different affinities for their partner transcription factors, and exert divergent, even opposing, biological roles [17, 20?9] (Fig. 1). Alternative splicing of SMRT, but not NCoR, has also been reported at many of the same locations in Xenopus as in mammals,?2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/),
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