Immobilization of Proteins in the Nucleolus by Ribosomal Intergenic Spacer Noncoding RNA

Timothy E. Audas, Mathieu D. Jacob, Stephen Lee

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

Cellular pathways are established and maintained by stochastic interactions of highly mobile molecules. The nucleolus plays a central role in the regulation of these molecular networks by capturing and immobilizing proteins. Here, we report a function for noncoding RNA (ncRNA) in the regulation of protein dynamics of key cellular factors, including VHL, Hsp70 and MDM2/PML. Stimuli-specific loci of the nucleolar intergenic spacer produce ncRNA capable of capturing and immobilizing proteins that encode a discrete peptidic code referred to as the nucleolar detention sequence (NoDS). Disruption of the NoDS/intergenic RNA interaction enables proteins to evade nucleolar sequestration and retain their dynamic profiles. Mislocalization of intergenic ncRNA triggers protein immobilization outside of the nucleolus, demonstrating that these ncRNA species can operate independently from the nucleolar architecture. We propose a model whereby protein immobilization by ncRNA is a posttranslational regulatory mechanism.

Original languageEnglish (US)
Pages (from-to)147-157
Number of pages11
JournalMolecular Cell
Volume45
Issue number2
DOIs
StatePublished - Jan 27 2012
Externally publishedYes

Fingerprint

Untranslated RNA
Immobilization
Proteins
Intergenic DNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Immobilization of Proteins in the Nucleolus by Ribosomal Intergenic Spacer Noncoding RNA. / Audas, Timothy E.; Jacob, Mathieu D.; Lee, Stephen.

In: Molecular Cell, Vol. 45, No. 2, 27.01.2012, p. 147-157.

Research output: Contribution to journalArticle

Audas, Timothy E. ; Jacob, Mathieu D. ; Lee, Stephen. / Immobilization of Proteins in the Nucleolus by Ribosomal Intergenic Spacer Noncoding RNA. In: Molecular Cell. 2012 ; Vol. 45, No. 2. pp. 147-157.
@article{f4ffc369cf2e48ba8b1f9c88c94045e1,
title = "Immobilization of Proteins in the Nucleolus by Ribosomal Intergenic Spacer Noncoding RNA",
abstract = "Cellular pathways are established and maintained by stochastic interactions of highly mobile molecules. The nucleolus plays a central role in the regulation of these molecular networks by capturing and immobilizing proteins. Here, we report a function for noncoding RNA (ncRNA) in the regulation of protein dynamics of key cellular factors, including VHL, Hsp70 and MDM2/PML. Stimuli-specific loci of the nucleolar intergenic spacer produce ncRNA capable of capturing and immobilizing proteins that encode a discrete peptidic code referred to as the nucleolar detention sequence (NoDS). Disruption of the NoDS/intergenic RNA interaction enables proteins to evade nucleolar sequestration and retain their dynamic profiles. Mislocalization of intergenic ncRNA triggers protein immobilization outside of the nucleolus, demonstrating that these ncRNA species can operate independently from the nucleolar architecture. We propose a model whereby protein immobilization by ncRNA is a posttranslational regulatory mechanism.",
author = "Audas, {Timothy E.} and Jacob, {Mathieu D.} and Stephen Lee",
year = "2012",
month = "1",
day = "27",
doi = "10.1016/j.molcel.2011.12.012",
language = "English (US)",
volume = "45",
pages = "147--157",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "2",

}

TY - JOUR

T1 - Immobilization of Proteins in the Nucleolus by Ribosomal Intergenic Spacer Noncoding RNA

AU - Audas, Timothy E.

AU - Jacob, Mathieu D.

AU - Lee, Stephen

PY - 2012/1/27

Y1 - 2012/1/27

N2 - Cellular pathways are established and maintained by stochastic interactions of highly mobile molecules. The nucleolus plays a central role in the regulation of these molecular networks by capturing and immobilizing proteins. Here, we report a function for noncoding RNA (ncRNA) in the regulation of protein dynamics of key cellular factors, including VHL, Hsp70 and MDM2/PML. Stimuli-specific loci of the nucleolar intergenic spacer produce ncRNA capable of capturing and immobilizing proteins that encode a discrete peptidic code referred to as the nucleolar detention sequence (NoDS). Disruption of the NoDS/intergenic RNA interaction enables proteins to evade nucleolar sequestration and retain their dynamic profiles. Mislocalization of intergenic ncRNA triggers protein immobilization outside of the nucleolus, demonstrating that these ncRNA species can operate independently from the nucleolar architecture. We propose a model whereby protein immobilization by ncRNA is a posttranslational regulatory mechanism.

AB - Cellular pathways are established and maintained by stochastic interactions of highly mobile molecules. The nucleolus plays a central role in the regulation of these molecular networks by capturing and immobilizing proteins. Here, we report a function for noncoding RNA (ncRNA) in the regulation of protein dynamics of key cellular factors, including VHL, Hsp70 and MDM2/PML. Stimuli-specific loci of the nucleolar intergenic spacer produce ncRNA capable of capturing and immobilizing proteins that encode a discrete peptidic code referred to as the nucleolar detention sequence (NoDS). Disruption of the NoDS/intergenic RNA interaction enables proteins to evade nucleolar sequestration and retain their dynamic profiles. Mislocalization of intergenic ncRNA triggers protein immobilization outside of the nucleolus, demonstrating that these ncRNA species can operate independently from the nucleolar architecture. We propose a model whereby protein immobilization by ncRNA is a posttranslational regulatory mechanism.

UR - http://www.scopus.com/inward/record.url?scp=84863012035&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84863012035&partnerID=8YFLogxK

U2 - 10.1016/j.molcel.2011.12.012

DO - 10.1016/j.molcel.2011.12.012

M3 - Article

C2 - 22284675

AN - SCOPUS:84863012035

VL - 45

SP - 147

EP - 157

JO - Molecular Cell

JF - Molecular Cell

SN - 1097-2765

IS - 2

ER -