Acute Heat Stress Leads to Reversible Aggregation of Nuclear Proteins into Nucleolar Rings in Fission Yeast

Reversible protein aggregation as cytoprotective mechanism against heat stress

“…In fission yeast, acute heat stress (42 ℃), which prevents bulk protein synthesis and blocks general mRNA metabolism (Cabrera et al 2020;Gallardo et al 2020;Ribeiro et al 1997), results in a dramatic reorganization of the nucleus. These nuclear architectural changes include nucleolar contraction and the formation of ring-shaped nucleolar aggregation centers, named Nucleolar Rings (NuR) (Gallardo et al 2020). NuRs assemblies contain a wide and functionally divergent group of nuclear factors, including factors involved in mRNA processing and export, nuclear pore complex (NPC) components, mRNA, chromatin-associated factors, and cell cycle regulators.…”

“…NuRs assemblies contain a wide and functionally divergent group of nuclear factors, including factors involved in mRNA processing and export, nuclear pore complex (NPC) components, mRNA, chromatin-associated factors, and cell cycle regulators. The formation of these assemblies is triggered by HSinduced unfolding and aggregation of proteins and RNAs (Gallardo et al 2020). While the aggregation of cell cycle factors at NuRs could contribute to the arrest of cell division observed under this extreme temperature, the rearrangement of the NPC and mRNA machinery could be responsible for the block of housekeeping mRNA metabolism and export and for the formation of a reservoir of messenger ribonucleoprotein (mRNPs) particles, which would be ready for export once stress conditions cease.…”

“…NuRs are formed by the rapid aggregation of multiple nuclear proteins, which remain mostly immobile, while the stress persists. However, when the stress is relieved, NuRs disaggregate and their multiple components relocate back to their functional localization (Gallardo et al 2020). This shows that fission yeast cells can modulate protein aggregation, turning deleterious protein aggregates into cytoprotective protein sequestering centers which contribute to maintain cellular homeostasis.…”

RTL8 promotes nuclear localization of UBQLN2 to subnuclear compartments associated with protein quality control

“…1F, middle panel) suggesting that it partitions into specific subnuclear organelles. The co-localization with UBQLN2, a known participant in protein degradation pathways, led us to investigate whether endogenous RTL8 resides in nucleoli or PML nuclear bodies, both of which have been implicated in nuclear PQC [27][28][29][30]. Unfortunately, commercial a-RTL8 antibodies do not stain endogenous RTL8 in HEK293 cells by immunofluorescence, thus we generated an a-RTL8A polyclonal rabbit antibody.…”

“…For example, in HD mouse models, UBQLN2 localizes to neuronal nuclei where it is thought to facilitate clearance of mutant Huntingtin [13][14][15]26]. Several membraneless organelles in the nucleus, notably nucleoli and PML bodies, have recently been implicated in nuclear PQC [27][28][29][30]. These subnuclear condensates undergo phase transitions from liquid-like to solid states and sequester stress-induced protein aggregates.…”