SMRTε, a corepressor variant, interacts with a restricted subset of nuclear receptors, including the retinoic acid receptors α and β

Brenda J. Mengeling, Michael L. Goodson, William Bourguet, Martin L. Privalsky

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The SMRT and NCoR corepressors bind to, and mediate transcriptional repression by, many nuclear receptors. Both SMRT and NCoR are expressed by alternative mRNA splicing, generating a series of structurally and functionally distinct corepressor " variants" We report that a splice variant of SMRT, SMRTε, recognizes a restricted subset of nuclear receptors. Unlike the other corepressor variants characterized, SMRTε possesses only a single receptor interaction domain (RID) and exhibits an unusual specificity for a subset of nuclear receptors that includes the retinoic acid receptors (RARs). The ability of the single RID in SMRTε to efficiently interact with RARs appears to be enhanced by a recently recognized β-strand/β-strand interaction between corepressor and receptor. We suggest that alternative mRNA splicing of corepressors can restrict their function to specific nuclear receptor partnerships, and we propose that this may serve to customize the transcriptional repression properties of different cell types for different biological purposes.

Original languageEnglish (US)
Pages (from-to)306-316
Number of pages11
JournalMolecular and Cellular Endocrinology
Volume351
Issue number2
DOIs
StatePublished - Apr 4 2012

Fingerprint

Nuclear Receptor Co-Repressor 2
Co-Repressor Proteins
Retinoic Acid Receptors
Cytoplasmic and Nuclear Receptors
Alternative Splicing
Messenger RNA

Keywords

  • β-Strand
  • Alternative-mRNA splicing
  • Corepressors
  • Nuclear receptors
  • Retinoic acid receptors
  • SMRT

ASJC Scopus subject areas

  • Endocrinology
  • Molecular Biology
  • Biochemistry

Cite this

SMRTε, a corepressor variant, interacts with a restricted subset of nuclear receptors, including the retinoic acid receptors α and β. / Mengeling, Brenda J.; Goodson, Michael L.; Bourguet, William; Privalsky, Martin L.

In: Molecular and Cellular Endocrinology, Vol. 351, No. 2, 04.04.2012, p. 306-316.

Research output: Contribution to journalArticle

Mengeling, Brenda J. ; Goodson, Michael L. ; Bourguet, William ; Privalsky, Martin L. / SMRTε, a corepressor variant, interacts with a restricted subset of nuclear receptors, including the retinoic acid receptors α and β. In: Molecular and Cellular Endocrinology. 2012 ; Vol. 351, No. 2. pp. 306-316.
@article{0a4b225ac0b140b5bd6fadcfbcbc6c52,
title = "SMRTε, a corepressor variant, interacts with a restricted subset of nuclear receptors, including the retinoic acid receptors α and β",
abstract = "The SMRT and NCoR corepressors bind to, and mediate transcriptional repression by, many nuclear receptors. Both SMRT and NCoR are expressed by alternative mRNA splicing, generating a series of structurally and functionally distinct corepressor {"} variants{"} We report that a splice variant of SMRT, SMRTε, recognizes a restricted subset of nuclear receptors. Unlike the other corepressor variants characterized, SMRTε possesses only a single receptor interaction domain (RID) and exhibits an unusual specificity for a subset of nuclear receptors that includes the retinoic acid receptors (RARs). The ability of the single RID in SMRTε to efficiently interact with RARs appears to be enhanced by a recently recognized β-strand/β-strand interaction between corepressor and receptor. We suggest that alternative mRNA splicing of corepressors can restrict their function to specific nuclear receptor partnerships, and we propose that this may serve to customize the transcriptional repression properties of different cell types for different biological purposes.",
keywords = "β-Strand, Alternative-mRNA splicing, Corepressors, Nuclear receptors, Retinoic acid receptors, SMRT",
author = "Mengeling, {Brenda J.} and Goodson, {Michael L.} and William Bourguet and Privalsky, {Martin L.}",
year = "2012",
month = "4",
day = "4",
doi = "10.1016/j.mce.2012.01.006",
language = "English (US)",
volume = "351",
pages = "306--316",
journal = "Molecular and Cellular Endocrinology",
issn = "0303-7207",
publisher = "Elsevier Ireland Ltd",
number = "2",

}

TY - JOUR

T1 - SMRTε, a corepressor variant, interacts with a restricted subset of nuclear receptors, including the retinoic acid receptors α and β

AU - Mengeling, Brenda J.

AU - Goodson, Michael L.

AU - Bourguet, William

AU - Privalsky, Martin L.

PY - 2012/4/4

Y1 - 2012/4/4

N2 - The SMRT and NCoR corepressors bind to, and mediate transcriptional repression by, many nuclear receptors. Both SMRT and NCoR are expressed by alternative mRNA splicing, generating a series of structurally and functionally distinct corepressor " variants" We report that a splice variant of SMRT, SMRTε, recognizes a restricted subset of nuclear receptors. Unlike the other corepressor variants characterized, SMRTε possesses only a single receptor interaction domain (RID) and exhibits an unusual specificity for a subset of nuclear receptors that includes the retinoic acid receptors (RARs). The ability of the single RID in SMRTε to efficiently interact with RARs appears to be enhanced by a recently recognized β-strand/β-strand interaction between corepressor and receptor. We suggest that alternative mRNA splicing of corepressors can restrict their function to specific nuclear receptor partnerships, and we propose that this may serve to customize the transcriptional repression properties of different cell types for different biological purposes.

AB - The SMRT and NCoR corepressors bind to, and mediate transcriptional repression by, many nuclear receptors. Both SMRT and NCoR are expressed by alternative mRNA splicing, generating a series of structurally and functionally distinct corepressor " variants" We report that a splice variant of SMRT, SMRTε, recognizes a restricted subset of nuclear receptors. Unlike the other corepressor variants characterized, SMRTε possesses only a single receptor interaction domain (RID) and exhibits an unusual specificity for a subset of nuclear receptors that includes the retinoic acid receptors (RARs). The ability of the single RID in SMRTε to efficiently interact with RARs appears to be enhanced by a recently recognized β-strand/β-strand interaction between corepressor and receptor. We suggest that alternative mRNA splicing of corepressors can restrict their function to specific nuclear receptor partnerships, and we propose that this may serve to customize the transcriptional repression properties of different cell types for different biological purposes.

KW - β-Strand

KW - Alternative-mRNA splicing

KW - Corepressors

KW - Nuclear receptors

KW - Retinoic acid receptors

KW - SMRT

UR - http://www.scopus.com/inward/record.url?scp=84857140413&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84857140413&partnerID=8YFLogxK

U2 - 10.1016/j.mce.2012.01.006

DO - 10.1016/j.mce.2012.01.006

M3 - Article

C2 - 22266197

AN - SCOPUS:84857140413

VL - 351

SP - 306

EP - 316

JO - Molecular and Cellular Endocrinology

JF - Molecular and Cellular Endocrinology

SN - 0303-7207

IS - 2

ER -