SMAUG2/SAMD4B REGULATES MESENQUIMAL DEVELOPMENT

THOMAS, MARÍA GABRIELA; PEREZ-PEPE; PLESSIS, ANNE; BOCCACCIO, GRACIELA L; MANSILLA, DAVID; FERNÁNDEZ ALVAREZ, ANA JULIA; PIMENTEL, JERÓNIMO

Buenos Aires

Congreso; Reunion Conjunta de Sociedades de Biociencias; 2017

Ourlaboratory described that Smaug1/2, a translational repressor that bindsspecific motifs termed Smaug recognition elements(SREs), forms liquid organellessimilar to Processing Bodies. Previously our group described that Smaug1/Samd4amodulates synaptic plasticity in rat hippocampus (Baez et al., J Cell Biol2011) and other authors reported that Smaug2/Samd4b directs early neuronaldifferentiation (Amadei etal., J Neurosci2015). In addition, Smaug1/Samd4a KO mouse show strong developmental defects ofmesenquimaltissues (bone, cartilage, muscle and fat). Our objective is to investigate howSmaug1 / 2 regulate mesenquimaldifferentiation. We used 3T3-L1 cell lines as a adipocyte differentiation modeland found that Smaug proteins forms liquid organelles,which are different from PBs. Strickingly, Smaug silencing inhibits celldifferentiation. We designed an algorithm to predict SREs and found severalpotential targets, relevant to this phenotype that are conserved in mouse andhuman. In particular Smaug KD prevents the up-regulation of key transcriptionfactors that govern cell differentiation. In particular, we found that theearly pro-developmental transcription factor C/EBP-β inhibitory isoform (LIP)is upregulated upon Smaug KD, which might explain the inhibitory phenotype