The 5′ → 3′ exoribonuclease XRN1/Pacman and its functions in cellular processes and development

• Published in: Wiley interdisciplinary reviews. RNA 2012-07, Vol.3 (4), p.455-468
• Main Authors: Jones, Christopher Iain, Zabolotskaya, Maria Vasilyevna, Newbury, Sarah Faith
• Format: Article
• Language: English
• Subjects: Animals; Crystal structure; DNA helicase; Drosophila Proteins - chemistry; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Enzymes; Eukaryotic Cells - metabolism; Exoribonucleases - chemistry; Exoribonucleases - genetics; Exoribonucleases - metabolism; Genes; Humans; Insects; Microtubule-Associated Proteins - chemistry; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; miRNA; mRNA turnover; Mutation; Protein turnover; Proteins; RNA Stability; RNA, Messenger - metabolism; RNA-binding protein; Stem cells; Wound healing
• ISSN: 1757-7004; 1757-7012
• DOI: 10.1002/wrna.1109

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. WIREs RNA 2012, 3:455–468. doi: 10.1002/wrna.1109 This article is categorized under: RNA Interactions with Proteins and Other Molecules > RNA–Protein Complexes RNA Turnover and Surveillance > Regulation of RNA Stability RNA in Disease and Development > RNA in Disease RNA in Disease and Development > RNA in Development