SLIRP, a small SRA binding protein, is a nuclear receptor corepressor

E.C. Hatchell; S.M. Colley; Dianne Beveridge; Michael Epis; Lisa Stuart; Keith Giles; A.D. Redfern; L.E.C. Miles; Andrew Barker; L.M. Macdonald; Peter Arthur; J.C. Lui; J.L. Golding; R.K. Mcculloch; C.B. Metcalf; J.A. Wilce; M.C.J. Wilce; R.B. Lanz; B.W. O'Malley; Peter Leedman

doi:10.1016/j.molcel.2006.05.024

SLIRP, a small SRA binding protein, is a nuclear receptor corepressor

E.C. Hatchell, S.M. Colley, Dianne Beveridge, Michael Epis, Lisa Stuart, Keith Giles, A.D. Redfern, L.E.C. Miles, Andrew Barker, L.M. Macdonald, Peter Arthur, J.C. Lui, J.L. Golding, R.K. Mcculloch, C.B. Metcalf, J.A. Wilce, M.C.J. Wilce, R.B. Lanz, B.W. O'Malley, Peter Leedman

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111 Citations (Scopus)

Abstract

Steroid receptor RNA activator (SRA), the only known RNA coactivator, augments transactivation by nuclear receptors (NRs). We identified SLIRP (SRA stem-loop interacting RNA binding protein) binding to a functional substructure of SRA, STR7. SLIRP is expressed in normal and tumor tissues, contains an RNA recognition motif (RRM), represses NR transactivation in a SRA- and FIRM-dependent manner, augments the effect of Tamoxifen, and modulates association of SRC-1 with SRA. SHARP, a FIRM-containing corepressor, also binds STR7, augmenting repression with SLIRP. SLIRP colocalizes with SKIP (Chr14q24.3), another NR coregulator, and reduces SKIP-potentiated NR signaling. SLIRP is recruited to endogenous promoters (pS2 and metallothionein), the latter in a SRA-dependent manner, while NCoR promoter recruitment is dependent on SLIRP. The majority of the endogenous SLIRP resides in the mitochondria. Our data demonstrate that SLIRP modulates NR transactivation, suggest it may regulate mitochondrial function, and provide mechanistic insight into interactions between SRA, SLIRP, SRC-1, and NCoR.

Original language	English
Pages (from-to)	657-668
Number of pages	12
Journal	Molecular Cell
Volume	22
Issue number	5
DOIs	https://doi.org/10.1016/j.molcel.2006.05.024
Publication status	Published - 9 Jun 2006

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10.1016/j.molcel.2006.05.024

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Hatchell, E. C., Colley, S. M., Beveridge, D., Epis, M., Stuart, L., Giles, K., Redfern, A. D., Miles, L. E. C., Barker, A., Macdonald, L. M., Arthur, P., Lui, J. C., Golding, J. L., Mcculloch, R. K., Metcalf, C. B., Wilce, J. A., Wilce, M. C. J., Lanz, R. B., O'Malley, B. W., & Leedman, P. (2006). SLIRP, a small SRA binding protein, is a nuclear receptor corepressor. Molecular Cell, 22(5), 657-668. https://doi.org/10.1016/j.molcel.2006.05.024

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title = "SLIRP, a small SRA binding protein, is a nuclear receptor corepressor",

abstract = "Steroid receptor RNA activator (SRA), the only known RNA coactivator, augments transactivation by nuclear receptors (NRs). We identified SLIRP (SRA stem-loop interacting RNA binding protein) binding to a functional substructure of SRA, STR7. SLIRP is expressed in normal and tumor tissues, contains an RNA recognition motif (RRM), represses NR transactivation in a SRA- and FIRM-dependent manner, augments the effect of Tamoxifen, and modulates association of SRC-1 with SRA. SHARP, a FIRM-containing corepressor, also binds STR7, augmenting repression with SLIRP. SLIRP colocalizes with SKIP (Chr14q24.3), another NR coregulator, and reduces SKIP-potentiated NR signaling. SLIRP is recruited to endogenous promoters (pS2 and metallothionein), the latter in a SRA-dependent manner, while NCoR promoter recruitment is dependent on SLIRP. The majority of the endogenous SLIRP resides in the mitochondria. Our data demonstrate that SLIRP modulates NR transactivation, suggest it may regulate mitochondrial function, and provide mechanistic insight into interactions between SRA, SLIRP, SRC-1, and NCoR.",

keywords = "Amino Acid Sequence, Animals, Base Sequence, Breast Neoplasms/metabolism, COS Cells, Chlorocebus aethiops, Cloning, Molecular, DNA-Binding Proteins, Female, HeLa Cells, Histone Acetyltransferases, Homeodomain Proteins/genetics, Humans, Mitochondria/metabolism, Molecular Sequence Data, Nuclear Proteins/genetics, Nuclear Receptor Co-Repressor 1, Nuclear Receptor Coactivator 1, Promoter Regions, Genetic, Protein Conformation, RNA, Long Noncoding, RNA, Untranslated/genetics, RNA-Binding Proteins/chemistry, Repressor Proteins/genetics, Sequence Alignment, Transcription Factors/genetics, Tumor Cells, Cultured",

author = "E.C. Hatchell and S.M. Colley and Dianne Beveridge and Michael Epis and Lisa Stuart and Keith Giles and A.D. Redfern and L.E.C. Miles and Andrew Barker and L.M. Macdonald and Peter Arthur and J.C. Lui and J.L. Golding and R.K. Mcculloch and C.B. Metcalf and J.A. Wilce and M.C.J. Wilce and R.B. Lanz and B.W. O'Malley and Peter Leedman",

year = "2006",

month = jun,

day = "9",

doi = "10.1016/j.molcel.2006.05.024",

language = "English",

volume = "22",

pages = "657--668",

journal = "Molecular Cell",

issn = "1097-2765",

publisher = "Cell Press",

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Hatchell, EC, Colley, SM, Beveridge, D , Epis, M , Stuart, L, Giles, K, Redfern, AD, Miles, LEC, Barker, A, Macdonald, LM, Arthur, P, Lui, JC, Golding, JL, Mcculloch, RK, Metcalf, CB, Wilce, JA, Wilce, MCJ, Lanz, RB, O'Malley, BW & Leedman, P 2006, 'SLIRP, a small SRA binding protein, is a nuclear receptor corepressor', Molecular Cell, vol. 22, no. 5, pp. 657-668. https://doi.org/10.1016/j.molcel.2006.05.024

TY - JOUR

T1 - SLIRP, a small SRA binding protein, is a nuclear receptor corepressor

AU - Hatchell, E.C.

AU - Colley, S.M.

AU - Beveridge, Dianne

AU - Epis, Michael

AU - Stuart, Lisa

AU - Giles, Keith

AU - Redfern, A.D.

AU - Miles, L.E.C.

AU - Barker, Andrew

AU - Macdonald, L.M.

AU - Arthur, Peter

AU - Lui, J.C.

AU - Golding, J.L.

AU - Mcculloch, R.K.

AU - Metcalf, C.B.

AU - Wilce, J.A.

AU - Wilce, M.C.J.

AU - Lanz, R.B.

AU - O'Malley, B.W.

AU - Leedman, Peter

PY - 2006/6/9

Y1 - 2006/6/9

N2 - Steroid receptor RNA activator (SRA), the only known RNA coactivator, augments transactivation by nuclear receptors (NRs). We identified SLIRP (SRA stem-loop interacting RNA binding protein) binding to a functional substructure of SRA, STR7. SLIRP is expressed in normal and tumor tissues, contains an RNA recognition motif (RRM), represses NR transactivation in a SRA- and FIRM-dependent manner, augments the effect of Tamoxifen, and modulates association of SRC-1 with SRA. SHARP, a FIRM-containing corepressor, also binds STR7, augmenting repression with SLIRP. SLIRP colocalizes with SKIP (Chr14q24.3), another NR coregulator, and reduces SKIP-potentiated NR signaling. SLIRP is recruited to endogenous promoters (pS2 and metallothionein), the latter in a SRA-dependent manner, while NCoR promoter recruitment is dependent on SLIRP. The majority of the endogenous SLIRP resides in the mitochondria. Our data demonstrate that SLIRP modulates NR transactivation, suggest it may regulate mitochondrial function, and provide mechanistic insight into interactions between SRA, SLIRP, SRC-1, and NCoR.

AB - Steroid receptor RNA activator (SRA), the only known RNA coactivator, augments transactivation by nuclear receptors (NRs). We identified SLIRP (SRA stem-loop interacting RNA binding protein) binding to a functional substructure of SRA, STR7. SLIRP is expressed in normal and tumor tissues, contains an RNA recognition motif (RRM), represses NR transactivation in a SRA- and FIRM-dependent manner, augments the effect of Tamoxifen, and modulates association of SRC-1 with SRA. SHARP, a FIRM-containing corepressor, also binds STR7, augmenting repression with SLIRP. SLIRP colocalizes with SKIP (Chr14q24.3), another NR coregulator, and reduces SKIP-potentiated NR signaling. SLIRP is recruited to endogenous promoters (pS2 and metallothionein), the latter in a SRA-dependent manner, while NCoR promoter recruitment is dependent on SLIRP. The majority of the endogenous SLIRP resides in the mitochondria. Our data demonstrate that SLIRP modulates NR transactivation, suggest it may regulate mitochondrial function, and provide mechanistic insight into interactions between SRA, SLIRP, SRC-1, and NCoR.

KW - Amino Acid Sequence

KW - Animals

KW - Base Sequence

KW - Breast Neoplasms/metabolism

KW - COS Cells

KW - Chlorocebus aethiops

KW - Cloning, Molecular

KW - DNA-Binding Proteins

KW - Female

KW - HeLa Cells

KW - Histone Acetyltransferases

KW - Homeodomain Proteins/genetics

KW - Humans

KW - Mitochondria/metabolism

KW - Molecular Sequence Data

KW - Nuclear Proteins/genetics

KW - Nuclear Receptor Co-Repressor 1

KW - Nuclear Receptor Coactivator 1

KW - Promoter Regions, Genetic

KW - Protein Conformation

KW - RNA, Long Noncoding

KW - RNA, Untranslated/genetics

KW - RNA-Binding Proteins/chemistry

KW - Repressor Proteins/genetics

KW - Sequence Alignment

KW - Transcription Factors/genetics

KW - Tumor Cells, Cultured

U2 - 10.1016/j.molcel.2006.05.024

DO - 10.1016/j.molcel.2006.05.024

M3 - Article

C2 - 16762838

SN - 1097-2765

VL - 22

SP - 657

EP - 668

JO - Molecular Cell

JF - Molecular Cell

IS - 5

ER -

SLIRP, a small SRA binding protein, is a nuclear receptor corepressor

Abstract

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