caa a22 4500 606177523 CHVBK 20210128100752.0 cr unu---uuuuu 210128e20150601xx s 000 0 eng 10.1007/s00018-015-1847-9 doi (NATIONALLICENCE)springer-10.1007/s00018-015-1847-9 The PRMT5 arginine methyltransferase: many roles in development, cancer and beyond [Elektronische Daten] [Nicole Stopa, Jocelyn Krebs, David Shechter] Post-translational arginine methylation is responsible for regulation of many biological processes. The protein arginine methyltransferase 5 (PRMT5, also known as Hsl7, Jbp1, Skb1, Capsuleen, or Dart5) is the major enzyme responsible for mono- and symmetric dimethylation of arginine. An expanding literature demonstrates its critical biological function in a wide range of cellular processes. Histone and other protein methylation by PRMT5 regulate genome organization, transcription, stem cells, primordial germ cells, differentiation, the cell cycle, and spliceosome assembly. Metazoan PRMT5 is found in complex with the WD-repeat protein MEP50 (also known as Wdr77, androgen receptor coactivator p44, or Valois). PRMT5 also directly associates with a range of other protein factors, including pICln, Menin, CoPR5 and RioK1 that may alter its subcellular localization and protein substrate selection. Protein substrate and PRMT5-MEP50 post-translation modifications induce crosstalk to regulate PRMT5 activity. Crystal structures of C. elegans PRMT5 and human and frog PRMT5-MEP50 complexes provide substantial insight into the mechanisms of substrate recognition and procession to dimethylation. Enzymological studies of PRMT5 have uncovered compelling insights essential for future development of specific PRMT5 inhibitors. In addition, newly accumulating evidence implicates PRMT5 and MEP50 expression levels and their methyltransferase activity in cancer tumorigenesis, and, significantly, as markers of poor clinical outcome, marking them as potential oncogenes. Here, we review the substantial new literature on PRMT5 and its partners to highlight the significance of understanding this essential enzyme in health and disease. Springer Basel, 2015 Protein arginine methyltransferase nationallicence Histones nationallicence Spliceosome nationallicence Development nationallicence Cancer nationallicence Stopa Nicole Department of Biological Sciences, University of Alaska Anchorage, 3211 Providence Drive, 99508, Anchorage, AK, USA aut Krebs Jocelyn Department of Biological Sciences, University of Alaska Anchorage, 3211 Providence Drive, 99508, Anchorage, AK, USA aut Shechter David Department of Biochemistry, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, 10461, Bronx, NY, USA aut Cellular and Molecular Life Sciences Springer Basel 72/11(2015-06-01), 2041-2059 1420-682X 72:11<2041 2015 72 18 https://doi.org/10.1007/s00018-015-1847-9 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 review-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00018-015-1847-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Stopa Nicole Department of Biological Sciences, University of Alaska Anchorage, 3211 Providence Drive, 99508, Anchorage, AK, USA aut NATIONALLICENCE 700 1- Krebs Jocelyn Department of Biological Sciences, University of Alaska Anchorage, 3211 Providence Drive, 99508, Anchorage, AK, USA aut NATIONALLICENCE 700 1- Shechter David Department of Biochemistry, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, 10461, Bronx, NY, USA aut NATIONALLICENCE 773 0- Cellular and Molecular Life Sciences Springer Basel 72/11(2015-06-01), 2041-2059 1420-682X 72:11<2041 2015 72 18