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

SummaryCellular 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.

► ncRNA emanate from stimuli-specific loci of the central region of the rDNA IGS ► IGSRNA mediates protein immobilization in response to environmental stimuli ► A discrete peptidic signal is recognized by IGSRNA to mediate immobilization ► Protein immobilization is a prevalent mechanism of posttranslational regulation