PNRC accumulates in the nucleolus by interaction with B23/nucleophosmin via its nucleolar localization sequence

Abstract

PNRC (proline-rich nuclear receptor coregulatory protein) was primarily identified as a coactivator of nuclear receptors (NRs) by our laboratory, which enhances NR-mediated transcription by RNA polymerase II. Recent study has shown that PNRC also stimulates RNA polymerase III-dependent transcription through interaction with the subunit RPC39 of RNA polymerase III. Here, we report that PNRC accumulates in the nucleolus and its depletion by small interfering RNA (siRNA) impairs pre-rRNA transcription by RNA polymerase I. We identified the sequence at position 94–101 (94PKKRRKKK101) of PNRC as its nucleolar localization sequence (NoLS). Fusion of this sequence to GFP directed GFP to the nucleolus. Characterization of the NoLS revealed that the stretches of six successive basic residues are sufficient to function as a NoLS. Through co-immunoprecipitation assays, we demonstrated that the NoLS is necessary and sufficient to mediate the association of PNRC with B23/nucleophosmin. Moreover, B23 depletion by siRNA disrupted the accumulation of PNRC in the nucleolus. Together, our study indicates that PNRC is a novel nucleolar protein that might be involved in regulation of pre-rRNA synthesis, and it localizes to the nucleolus by interaction with B23 via its NoLS. Our study also suggests that the stretches of six successive basic residues (lysine and/or arginine) function as NoLS.

Identification and Characterization of Nuclear and Nucleolar Localization Signals in the Adeno-Associated Virus Serotype 2 Assembly-Activating Protein

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Identification of CHD7S as a novel splicing variant of CHD7 with functions similar and antagonistic to those of the full‐length CHD7L

“…A; Mongelard & Bouvet ; Wang et al . ). In contrast, EGFP‐CHD7 L was broadly localized in both the nucleolus and nucleoplasm (Fig.…”

Identification of Polyproline II Regions Derived From the Proline‐Rich Nuclear Receptor Coactivators PNRC and PNRC2: New Insights for ERα Coactivator Interactions

“…PNRC and PNRC2 are nuclear receptor coactivators operating after translocation of the receptor into the nucleus . PNRC interferes with different nuclear proteins such as nuclear hormone receptors including ERα and the polymerase III subunit RPC39 .…”