MLOs containing Smaug RBP regulates mitochondrial function

FERNÁNDEZ ALVAREZ, ANA JULIA

Encuentro; RNA 2021; 2021

Smaug is a conserved translational repressor thatrecognizes specific RNA motifs present in a large number of mRNAs, includingnuclear transcripts that encode mitochondrial enzymes. Here we show that thesimultaneous loss of function of mammalian Smaug1/Samd4a and Smaug2/Samd4b affectsmitochondrial activity and mitochondrial network morphology. Smaug orthologs wereshown to form membraneless organelles (MLOs) in several organisms and celltypes, and we found that Smaug MLOs frequently contact mitochondria. Singlemolecule FISH reveal that transcripts that encode SDHB and Uqcrc1 associatewith Smaug1 MLOs. In addition, defective Smaug1 MLO formation brought about bydeletion of relevant protein regions affects mitochondrial activity. Finally,rotenone and metformin but not the uncoupler CCCP rapidly induce Smaug MLO dissolutionand the release of bounded mRNAs. We propose that Smaug MLOs respond to changesin the energetic metabolism to coordinate the expression of mRNAs that encode keymitochondrial proteins.