Overexpression of SUMO perturbs the growth and development of Caenorhabditis elegans

Abstract

Small ubiquitin-related modifiers (SUMOs) are important regulator proteins. Caenorhabditis elegans contains a single SUMO ortholog, SMO-1, necessary for the reproduction of C. elegans. In this study, we constructed transgenic C. elegans strains expressing human SUMO-1 under the control of pan-neuronal (aex-3) or pan-muscular (myo-4) promoter and SUMO-2 under the control of myo-4 promoter. Interestingly, muscular overexpression of SUMO-1 or -2 resulted in morphological changes of the posterior part of the nematode. Movement, reproduction and aging of C. elegans were perturbed by the overexpression of SUMO-1 or -2. Genome-wide expression analyses revealed that several genes encoding components of SUMOylation pathway and ubiquitin-proteasome system were upregulated in SUMO-overexpressing nematodes. Since muscular overexpression of SMO-1 also brought up reproductive and mobility perturbations, our results imply that the phenotypes were largely due to an excess of SUMO, suggesting that a tight control of SUMO levels is important for the normal development of multicellular organisms.

Epigenetic Mechanisms of Longevity and Aging

“…Ubiquitylation of DAF-16 (discussed later), an important longevity protein causes shorter lifespan in worms (Li et al, 2007). SUMO expression is increased in old rats and senescent fibroblasts and overexpression of SUMO causes premature aging in worms (Rytinki et al, 2011). SUMO-induced senescence acts through an interconnected network of pathways that involve sumoylation of proteins in promyelocytic leukemia (PML) nuclear bodies, p53/pRb and its interacting proteins to impact senescence-specific transcription programs (Ivanschitz et al, 2013).…”

PML, SUMOylation, and Senescence

“…In old rats and senescent fibroblasts in culture, SUMO expression increases with aging and hyper-SUMOylated protein forms become more abundant (67–69). Overexpression of SUMO-1 or SUMO-2 in Caenorhabditis elegans led to shortened life span and reproduction disorder (70), while loss of SUMOylation process resulted in severe zebrafish development defects (71) or misdifferentiation and microtumors development of hematopoietic progenitors in Drosophila (72). Altogether, these experiments confirm the crucial role of SUMO in development and tumor suppression.…”

Structural and functional analysis of SMO-1, the SUMO homolog in Caenorhabditis elegans

“…Hence, SMO-1 appears to have combined the features of SUMO1 and SUMO2. Homozygous worms with SMO-1 knockdown have reproductive defects[ 27 , 55 ]. It is not surprising that expression of SUMO1 or SUMO2 can partially rescue the absence of SMO-1 in reproduction[ 55 ].…”

“…Homozygous worms with SMO-1 knockdown have reproductive defects[ 27 , 55 ]. It is not surprising that expression of SUMO1 or SUMO2 can partially rescue the absence of SMO-1 in reproduction[ 55 ]. As the single SUMO protein has to be recognised by downstream effector protein of multiple pathways in C .…”