Active nuclear-cytoplasmic transport of several proteins and RNAs is facilitated by nuclear import and export receptors. Exportin 1 (XPO-1/XPO1/CRM1) is one such conserved receptor that aids nuclear export of a few mRNA and over 200 proteins including pre-ribosomal subunits, transcription factors, tumor suppressors, and oncoproteins. Previously, we had shown that genetic and pharmacological inhibition of XPO-1 conferred proteostatic benefits and enhanced lifespan in nematodes by transcriptional upregulation of autophagy via the transcription factor HLH-30/TFEB. Since XPO-1 is a major export receptor, we sought to characterize the nucleo-cytoplasmic distribution of proteins upon
xpo-1 silencing. Proteomic analysis of nuclear and non-nuclear (cytoplasmic) fractions of worms upon
xpo-1 RNAi by TMT-MS revealed repartitioning of several proteins involved in ribosome biogenesis, translation initiation, mRNA functions, and proteostasis. We also found transcriptional downregulation of ribosomal genes and a global reduction of protein synthesis by RNA-sequencing and polysome profiling, respectively. Additionally, the size of nucleoli, the hubs of rRNA synthesis inside the nucleus, and levels of nucleolar protein fibrillarin were significantly decreased, in line with recent reports on long-lived nematodes. Probing altered nucleolar dynamics further, we uncovered RPL-11.1, a ribosomal large subunit protein that has a role in nucleolar stress response, to be repartitioned to the nucleus in
xpo-1 RNAi nematodes. We found that RPL-11.1 modulates nucleolar size in an LGG-1-dependent fashion, i.e., nuclear RPL-11.1 levels and nucleolar size increase when the autophagosome protein, LGG-1/GABARAP, is silenced. Our results also indicate an interaction between RPL-11.1 and LGG-1, highlighting a novel link between two convergent hallmarks of aging, nucleolar size and proteostasis. Furthermore, silencing
rpl-11.1 in nematodes expressing Alzheimer's Disease protein, AB, in muscles, significantly reduced paralysis suggesting proteostatic benefits of reduced RPL-11.1 levels. Altogether, our data uncover that autophagy protein LGG-1/GABARAP is a key modulator of nucleolar function and lifespan by surveilling ribosomal subunits in the nucleus.