PMID- 22383165 OWN - NLM STAT- MEDLINE DCOM- 20121009 LR - 20211021 IS - 1757-7012 (Electronic) IS - 1757-7004 (Linking) VI - 3 IP - 4 DP - 2012 Jul-Aug TI - The 5' --> 3' exoribonuclease XRN1/Pacman and its functions in cellular processes and development. PG - 455-68 LID - 10.1002/wrna.1109 [doi] AB - XRN1 is a 5' --> 3' processive exoribonuclease that degrades mRNAs after they have been decapped. It is highly conserved in all eukaryotes, including homologs in Drosophila melanogaster (Pacman), Caenorhabditis elegans (XRN1), and Saccharomyces cerevisiae (Xrn1p). As well as being a key enzyme in RNA turnover, XRN1 is involved in nonsense-mediated mRNA decay and degradation of mRNAs after they have been targeted by small interfering RNAs or microRNAs. The crystal structure of XRN1 can explain its processivity and also the selectivity of the enzyme for 5' monophosphorylated RNA. In eukaryotic cells, XRN1 is often found in particles known as processing bodies (P bodies) together with other proteins involved in the 5' --> 3' degradation pathway, such as DCP2 and the helicase DHH1 (Me31B). Although XRN1 shows little specificity to particular 5' monophosphorylated RNAs in vitro, mutations in XRN1 in vivo have specific phenotypes suggesting that it specifically degrades a subset of RNAs. In Drosophila, mutations in the gene encoding the XRN1 homolog pacman result in defects in wound healing, epithelial closure and stem cell renewal in testes. We propose a model where specific mRNAs are targeted to XRN1 via specific binding of miRNAs and/or RNA-binding proteins to instability elements within the RNA. These guide the RNA to the 5' core degradation apparatus for controlled degradation. CI - Copyright (c) 2012 John Wiley & Sons, Ltd. FAU - Jones, Christopher Iain AU - Jones CI AD - Brighton and Sussex Medical School, University of Sussex, Falmer, Brighton, UK. FAU - Zabolotskaya, Maria Vasilyevna AU - Zabolotskaya MV FAU - Newbury, Sarah Faith AU - Newbury SF LA - eng GR - BB/G002754/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom GR - BBI021345/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom GR - BB/I007989/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20120301 PL - United States TA - Wiley Interdiscip Rev RNA JT - Wiley interdisciplinary reviews. RNA JID - 101536955 RN - 0 (Drosophila Proteins) RN - 0 (Microtubule-Associated Proteins) RN - 0 (RNA, Messenger) RN - EC 3.1.- (Exoribonucleases) RN - EC 3.1.- (pcm protein, Drosophila) RN - EC 3.1.13.1 (XRN1 protein, human) SB - IM MH - Animals MH - Drosophila Proteins/chemistry/genetics/*metabolism MH - Eukaryotic Cells/metabolism MH - Exoribonucleases/chemistry/genetics/*metabolism MH - Humans MH - Microtubule-Associated Proteins/chemistry/genetics/*metabolism MH - *RNA Stability MH - RNA, Messenger/*metabolism EDAT- 2012/03/03 06:00 MHDA- 2012/10/10 06:00 CRDT- 2012/03/03 06:00 PHST- 2012/03/03 06:00 [entrez] PHST- 2012/03/03 06:00 [pubmed] PHST- 2012/10/10 06:00 [medline] AID - 10.1002/wrna.1109 [doi] PST - ppublish SO - Wiley Interdiscip Rev RNA. 2012 Jul-Aug;3(4):455-68. doi: 10.1002/wrna.1109. Epub 2012 Mar 1.