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FAM46 proteins are novel eukaryotic non-canonical poly (A) polymerases

Kuchta, Krzysztof and Muszewska, Anna and Knizewski, Lukasz and Steczkiewicz, Kamil and Wyrwicz, Lucjan and Pawłowski, Krzysztof and Rychlewski, Leszek and Ginalski, Krzysztof (2016) FAM46 proteins are novel eukaryotic non-canonical poly (A) polymerases. Nucleic acids research . ISSN 1362-4962


Official URL: https://nar.oxfordjournals.org/content/early/2016/...


FAM46 proteins, encoded in all known animal genomes, belong to the nucleotidyltransferase (NTase) fold superfamily. All four human FAM46 paralogs (FAM46A, FAM46B, FAM46C, FAM46D) are thought to be involved in several diseases, with FAM46C reported as a causal driver of multiple myeloma; however, their exact functions remain unknown. By using a combination of various bioinformatics analyses (e.g. domain architecture, cellular localization) and exhaustive literature and database searches (e.g. expression profiles, protein interactors), we classified FAM46 proteins as active non-canonical poly(A) polymerases, which modify cytosolic and/or nuclear RNA 3′ ends. These proteins may thus regulate gene expression and probably play a critical role during cell differentiation. A detailed analysis of sequence and structure diversity of known NTases possessing PAP/OAS1 SBD domain, combined with state-of-the-art comparative modelling, allowed us to identify potential active site residues responsible for catalysis and substrate binding. We also explored the role of single point mutations found in human cancers and propose that FAM46 genes may be involved in the development of other major malignancies including lung, colorectal, hepatocellular, head and neck, urothelial, endometrial and renal papillary carcinomas and melanoma. Identification of these novel enzymes taking part in RNA metabolism in eukaryotes may guide their further functional studies.

Item Type:Article
Subjects:Q Science > QH Natural history > QH301 Biology
Divisions:Department of Microbial Biochemistry
ID Code:1178
Deposited By: dr Anna Muszewska
Deposited On:26 Apr 2016 09:49
Last Modified:26 Apr 2016 09:49

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