SMAUG DRIVES ADIPOCYTE DIFFERENTIATION BY REGULATING C/EBPΒ TRANSLATION

FERNÁNDEZ ALVAREZ, ANA JULIA; THOMAS, MARÍA GABRIELA; PIMENTEL, JERÓNIMO; BOCCACCIO, GRACIELA L

Buenos Aires

Encuentro; Xth Meeting of the Latin American Society for Developmental Biology; 2019

LASDB

Smaug is a translational repressor that binds specific RNA motifs and form membraneless organelles (MLOs) similar to Processing Bodies (PBs), termed S-bodies. In neurons, the S-bodies localize at dendrites and respond to specific synaptic stimuli, dissolving and releasing transcripts to allow their translation (Baez et al., J Cell Biol 2011; Pimentel & Boccaccio 2014; Luchelli et al. J Cell Sci, 2015). In addition, Smaug function seems important in other cell types. Smaug1/Samd4a KO mice show strong developmental defects of mesenchymal tissues, namely bone, cartilage, muscle and fat. Here we show that Smaug forms cytosolic S-bodies in 3T3L1 that contain repressed mRNAs. Smaug expression increases during adipocyte differentiation and mediates its differentiation. Smaug KD in 3T3L1 cells affects several molecular and cellular markers of adipogenesis, including the accumulation of lipid droplets and the expression of C/EBPβ, a key transcription factor that regulates adipogenesis. The alternative translation of C/EBPβ mRNA generates two proteins with antagonistic effect and the regulation of alternative translation of C/EBPβ is poorly described. A pro-adipogenic C/EBPβ variant is translated from an early AUG and the translation of a downstream AUG brings about an inhibitory C/EBPβ isoform. We found that Smaug knockdown affects the expression of these two protein isoforms, and the effect appears to be direct as Smaug binds C/EBPβ mRNA.