Sonic Hedgehog pathway regulates the post-transcriptional regulator Smaug1

PIMENTEL, J; PEREZ PEPE, M; FERNANDEZ-ALVAREZ AJ; PASCUAL M; THOMAS MG; ARGUELLES, C; PLESSIS, A; BOCCACCIO GL

Mar del Plata

Congreso; SAIB (Sociedad Argentina de Investigaciones Bioquímicas y Biología Molecular) 2015; 2015

SAIB (Sociedad Argentina de Investigaciones Bioquímicas y Biología Molecular)

Mammalian mSmaug1 is a mRNArepressor involved in translational regulation in hippocampal synapses and thatforms cytoplasmic silencing foci (S-foci) similar to Stress Granulesand Processing Bodies (Baez and Boccaccio, JBC 2005; Baez et al., JCB2011). Both Drosophila and mammalianSmaug repress reporter mRNAs carrying specific motifs termedSmaug-Recognition-Elements (SREs), which consist of a stem-loop with thesequence CNGGN(0-8). Using an ad hoc MATLABalgorithm, we carried out an in silico search to identify mammalian transcriptscarrying SREs. We found that several human transcripts linked to glycolysis,lipid metabolism and mitochondrial function are potential Smaug targets,and similar results were reported in Drosophila. Mice carrying amutation in Smaug1 present a phenotype similar to that of SonicHedgehog (Shh) mutants. The Shh pathway is a major signaling pathwayand we found that pharmacological manipulation of  Shh affects S- fociformation. These results suggest that Smaug repression is regulated by Shh,likely affecting the expression of key cellular transcripts.