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Žaja, R.* ; Aydin, G.* ; Lippok, B.E.* ; Feederle, R. ; Lüscher, B.* ; Feijs, K.L.H.*

Comparative analysis of MACROD1, MACROD2 and TARG1 expression, localisation and interactome.

Sci. Rep. 10:8286 (2020)
Publ. Version/Full Text DOI
Open Access Gold
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The posttranslational modification ADP-ribosylation is involved in many cellular processes, with distinct roles for poly- and mono(ADP-ribosyl)ation (PAR- and MARylation, respectively). Reversibility of intracellular MARylation was demonstrated with the discovery of MACROD1, MACROD2 and TARG1, three macrodomain-containing enzymes capable of reversing MARylation of proteins and RNA. While the three enzymes have identical activities in vitro, their roles in cells are unclear and published data are partially contradictory, possibly due to a lack of validated reagents. We developed monoclonal antibodies to study these proteins and analysed their tissue distribution and intracellular localisation. MACROD1 is most prevalent in mitochondria of skeletal muscle, MACROD2 localises to nucleo- and cytoplasm and is found so far only in neuroblastoma cells, whereas the more ubiquitously expressed TARG1 is present in nucleoplasm, nucleolus and stress granules. Loss of MACROD1 or loss of TARG1 leads to disruption of mitochondrial or nucleolar morphology, respectively, hinting at their importance for these organelles. To start elucidating the underlying mechanisms, we have mapped their interactomes using BioID. The cellular localisation of interactors supports the mitochondrial, nucleolar and stress granule localisation of MACROD1 and TARG1, respectively. Gene ontology analysis suggests an involvement of MACROD1 and TARG1 in RNA metabolism in their respective compartments. The detailed description of the hydrolases' expression, localisation and interactome presented here provides a solid basis for future work addressing their physiological function in more detail.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Mono-adp-ribosyltransferase; Chikungunya Virus; Ribosylation; Proteins; Domain; Lrp16; Macrodomains; Replication; Activation; Stress
ISSN (print) / ISBN 2045-2322
e-ISSN 2045-2322
Quellenangaben Volume: 10, Issue: 1, Pages: , Article Number: 8286 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) CF Monoclonal Antibodies (CF-MAB)