Diverse Functions of mRNA Metabolism Factors in Stress Defense and Aging of Caenorhabditis elegans

Abstract

Processing bodies (PBs) and stress granules (SGs) are related, cytoplasmic RNA-protein complexes that contribute to post-transcriptional gene regulation in all eukaryotic cells. Both structures contain translationally repressed mRNAs and several proteins involved in silencing, stabilization or degradation of mRNAs, especially under environmental stress. Here, we monitored the dynamic formation of PBs and SGs, in somatic cells of adult worms, using fluorescently tagged protein markers of each complex. Both complexes were accumulated in response to various stress conditions, but distinct modes of SG formation were induced, depending on the insult. We also observed an age-dependent accumulation of PBs but not of SGs. We further showed that direct alterations in PB-related genes can influence aging and normal stress responses, beyond their developmental role. In addition, disruption of SG-related genes had diverse effects on development, fertility, lifespan and stress resistance of worms. Our work therefore underlines the important roles of mRNA metabolism factors in several vital cellular processes and provides insight into their diverse functions in a multicellular organism.

Reduced Insulin/IGF-1 Signaling Restores the Dynamic Properties of Key Stress Granule Proteins during Aging

“…Similarly, heat shock in C. elegans caused PAB-1 and TIAR-2 to form stress granules (Figures 2A and 2C; Figure S4A) (Murakami et al., 2012, Rousakis et al., 2014). When co-expressed, PAB-1 and TIAR-2 localized to the same stress granules (Figure S4B).…”

Neuronal function of the mRNA decapping complex determines survival ofCaenorhabditis elegansat high temperature through temporal regulation of heterochronic gene expression

“…Previously, we have shown that disruption of dcap-1 or dcap-2 genes, encoding the subunits of the mRNA decapping complex in worms, significantly shortens the extremely long life of class I daf-2(1368) mutants and reduces their resistance to stress [39]. Intriguingly though, the double mutant daf-2(e1368);dcap-1(tm3163) or daf-2(e1368);dcap-2(ok2023) animals were found to display increased levels of dauer arrest at the permissive temperature of 22°C compared with daf-2 single mutants (figure 1 a ).…”

“…This was also true for the class II daf-2(e1370) hypomorphic allele (figure 1 a ). The dcap-1(tm3163) phenotype proved to be less penetrant than the null dcap-2(ok2023) owing to an out-of-frame deletion that completely eliminates dcap-1 activity at 25°C, but retains a weak residual activity at lower temperatures [39]. At 22°C or 25°C, single decapping mutants did not form any dauers on their own, in the presence of food.…”

“…In C. elegans , lin-4 and its targets lin-14 and lin-28 are expressed in several cell types, such as hypodermis, muscles and neurons [20,21], resembling the expression pattern of dcap-1 that we had previously determined using a translational dcap-1::gfp reporter [39]. To identify the major site of DCAP-1 function in developmental decisions at high temperature, we scored the percentage of arrested larvae in a series of transgenic animals expressing dcap-1::gfp in selective tissues.…”

Cytoplasmic LSM-1 protein regulates stress responses through the insulin/IGF-1 signaling pathway in Caenorhabditis elegans

“…For the co-localization experiments, CER157 animals expressing integrated copies of LSM-1::GFP were injected with a mix containing 80 ng/μL of a RFP::TIAR-1 construct (Rousakis et al 2014) and 20 ng/μL of the linearized roller marker pRF4 [rol-6(su1006)]. Transcriptional reporters, described in the Supplemental Material, were constructed by PCR fusion (Hobert 2002).…”