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SUMMARY:The role of Selenoprotein O in mitochondrial signaling - Anju Sree
 latha Ph.D. Assistant Professor\, Department of Physiology\, UT Southweste
 rn Center for Mineral Metabolism and Clinical Research
DTSTART:20260223T123000Z
DTEND:20260223T133000Z
UID:TALK243937@talks.cam.ac.uk
CONTACT:Simona Valeviciute
DESCRIPTION:Abstract:  Protein AMPylation\, the covalent addition of adeno
 sine monophosphate (AMP) to protein substrates\, has been known as a post 
 translational modification for over 50 years.\n\nRelative to PTMs such as 
 phosphorylation\, the breadth of protein AMPylation is underexplored. To a
 ddress this gap\, we developed an enrichment technique to isolate and stud
 y AMPylated proteins using a nucleotide-binding protein\, hinT. Using cryo
 -EM guided mutagenesis\, we optimized enrichment to identify novel substra
 tes of the mitochondrial AMPylase\, Selenoprotein O. We show that mammalia
 n Selenoprotein O regulates metabolic flux through AMPylation of key mitoc
 hondrial proteins including glutamate dehydrogenase and pyruvate dehydroge
 nase.\n\nOur findings highlight the broader significance of AMPylation\, a
 n emerging post translational modification with critical roles in signal t
 ransduction and disease pathology. Remarkably\, Selenoprotein O-mediated A
 MPylation is conserved in bacteria and humans\, yet the enzyme that remove
 s the AMP from modified proteins remains unknown.\n\nUsing our newly devel
 oped enrichment platform\, we identified that the ribonuclease\, RNase Z\,
  is both necessary and sufficient to catalyze deAMPylation of AMPylated su
 bstrates. These results establish RNase Z as a moonlighting enzyme with pr
 eviously unrecognized functional roles beyond tRNA processing\, expanding 
 our understanding of its biological significance. Identification of an evo
 lutionarily conserved deAMPylase highlights the importance of reversible A
 MPylation as a biological regulatory mechanism\, akin to well-studied post
  translational modifications such as protein phosphorylation.\n\nTogether\
 , our discovery of the mitochondrial deAMPylase and our novel enrichment s
 trategy lay the foundation for defining the role of AMPylation in cellular
  signaling and highlight the central role of Selenoprotein O in mitochondr
 ial biology.\n\n 
LOCATION:CRUK CI Lecture Theatre
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