Nucleolar stress induced the formation of a nucleolar stress body via the NOSR-1/NUMR-1 axis inCaenorhabditis elegans

Abstract

Environmental stimuli not only alter gene expression profiles but also induce structural changes in cells. How distinct nuclear bodies respond to cellular stress is poorly understood. Here, we identified a new subnuclear organelle named the nucleolar stress body (NoSB), the formation of which was induced by the inhibition of rRNA transcription or inactivation of rRNA processing and maturation inC. elegans. NoSB did not colocalize with other previously described subnuclear organelles. We conducted forward genetic screening and identified a new bZIP transcription factor, namednucleolarstress response-1 (NOSR-1), that is required for NoSB formation. The inhibition of rRNA transcription or inactivation of rRNA processing and maturation increasednosr-1expression. By using transcriptome analysis of wild-type animals subjected to different nucleolar stress conditions andnosr-1mutants, we identified that the SR-like protein NUMR-1 (nuclear localized metal responsive) is the target of NOSR-1. Interestingly, NUMR-1 is a component of NoSB and itself per se is required for the formation of NoSB. We concluded that the NOSR-1/NUMR-1 axis likely responds to nucleolar stress and mediates downstream stress-responsive transcription programs and subnuclear morphology alterations inC. elegans.