RGS12TS-S localizes at nuclear matrix-associated subnuclear structures and represses transcription: Structural requirements for subnuclear targeting and transcriptional repression

Tapan K. Chatterjee, Rory A. Fisher

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

RGS12TS-S, an 1,157-amino-acid RGS protein (regulator of G protein signaling), is a nuclear protein that exhibits a unique pattern of subnuclear organization into nuclear foci or dots when expressed endogenously or ectopically. We now report that RGS12TS-S is a nuclear matrix protein and identify structural determinants that target this protein to the nuclear matrix and to discrete subnuclear sites. We also determine the relationship between RGS12TS-S-decorated nuclear dots and known subnuclear domains involved in control of gene expression and provide the first evidence that RGS12TS-S is functionally involved in the regulation of transcription and cell cycle events. A novel nuclear matrix-targeting sequence was identified that is distinct from a second novel motif needed for targeting RGS12TS-S to nuclear dots. RGS12TS-S nuclear dots were distinct from Cajal bodies, SC-35 domains, promyelocytic leukemia protein nuclear bodies, Polycomb group domains, and DNA replication sites. However, RGS12TS-S inhibited S-phase DNA synthesis in various tumor cell lines independently of Rb and p53 proteins, and its prolonged expression promoted formation of multinucleated cells. Expression of RGS12TS-S dramatically reduced bromo-UTP incorporation into sites of transcription. RGS12TS-S, when tethered to a Gal4 DNA binding domain, dramatically inhibited basal transcription from a Gal4-E1b TATA promoter in a histone deacetylase-independent manner. Structural analysis revealed a role for the unique N-terminal domain of RGS12TS-S in its transcriptional repressor and cell cycle-regulating activities and showed that the RGS domain was dispensable for these functions. These results provide novel insights into the structure and function of RGS12TS-S in the nucleus and demonstrate that RGS12TS-S possesses biological activities distinct from those of other members of the RGS protein family.

Original languageEnglish (US)
Pages (from-to)4334-4345
Number of pages12
JournalMolecular and Cellular Biology
Volume22
Issue number12
DOIs
StatePublished - Jun 5 2002

Fingerprint

RGS Proteins
Nuclear Matrix-Associated Proteins
Nuclear Matrix
Cell Cycle
Retinoblastoma Protein
Uridine Triphosphate
Histone Deacetylases
DNA
Nuclear Proteins
Tumor Cell Line
DNA Replication
S Phase
Gene Expression
Amino Acids

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

RGS12TS-S localizes at nuclear matrix-associated subnuclear structures and represses transcription : Structural requirements for subnuclear targeting and transcriptional repression. / Chatterjee, Tapan K.; Fisher, Rory A.

In: Molecular and Cellular Biology, Vol. 22, No. 12, 05.06.2002, p. 4334-4345.

Research output: Contribution to journalArticle

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