The nucleolus, a dynamic nuclear compartment long regarded as the cell ribosome factory, is emerging as an important player in the regulation of cell survival and recovery from stress. In larger eukaryotes, the stress-induced transcriptional response is mediated by a family of heat-shock transcription factors. Among these, HSF1, considered the master regulator of stress-induced transcriptional responses, controls the expression of cytoprotective heat shock proteins (HSPs), molecular chaperones/cochaperones constituting a major component of the cell protein quality control machinery essential to circumvent stress-induced degradation and aggregation of misfolded proteins. Herein we identify human NF-κB repressing factor (NKRF) as a nucleolar HSP essential for nucleolus homeostasis and cell survival under proteotoxic stress. NKRF acts as a thermosensor translocating from the nucleolus to the nucleoplasm during heat stress; nucleolar pools are replenished during recovery upon HSF1-mediated NKRF resynthesis. Silencing experiments demonstrate that NKRF is an unconventional HSP crucial for correct ribosomal RNA (rRNA) processing and preventing aberrant rRNA precursors and discarded fragment accumulation. These effects are mediated by NKRF interaction with the 5'-to-3' exoribonuclease XRN2, a key coordinator of multiple pre-rRNA cleavages, driving mature rRNA formation and discarded rRNA decay. Under stress conditions, NKRF directs XRN2 nucleolus/nucleoplasm trafficking, controlling 5'-to-3' exoribonuclease nucleolar levels and regulating rRNA processing. Our study reveals a different aspect of rRNA biogenesis control in human cells and sheds light on a sophisticated mechanism of nucleolar homeostasis surveillance during stress.
Coccia, M., Rossi, A., Riccio, A., Trotta, L., & Santoro, M.G. (2017). Human NF-κB repressing factor acts as a stress-regulated switch for ribosomal RNA processing and nucleolar homeostasis surveillance. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 114(5), 1045-1050.
|Tipologia:||Articolo su rivista|
|Citazione:||Coccia, M., Rossi, A., Riccio, A., Trotta, L., & Santoro, M.G. (2017). Human NF-κB repressing factor acts as a stress-regulated switch for ribosomal RNA processing and nucleolar homeostasis surveillance. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 114(5), 1045-1050.|
|Altre informazioni significative:||This article was selected to be highlighted in the Editors’ Choice section of Science Signaling (Sci. Signal. 10, 465. doi: 10.1126/scisignal.aam9083).|
|IF:||Con Impact Factor ISI|
|Settore Scientifico Disciplinare:||Settore MED/07 - Microbiologia e Microbiologia Clinica|
|Revisione (peer review):||Esperti anonimi|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1073/pnas.1616112114|
|Stato di pubblicazione:||Pubblicato|
|Data di pubblicazione:||2017|
|Titolo:||Human NF-κB repressing factor acts as a stress-regulated switch for ribosomal RNA processing and nucleolar homeostasis surveillance|
|Autori:||Coccia, M; Rossi, A; Riccio, A; Trotta, L; Santoro, MG|
|Appare nelle tipologie:||01 - Articolo su rivista|