title: The RtcB RNA ligase is an essential component of the metazoan unfolded protein response.
abstract: RNA ligation can regulate RNA function by altering RNA sequence, structure and coding potential. For example, the function of XBP1 in mediating the unfolded protein response requires RNA ligation, as does the maturation of some tRNAs. Here, we describe a novel in vivo model in Caenorhabditis elegans for the conserved RNA ligase RtcB and show that RtcB ligates the xbp-1 mRNA during the IRE-1 branch of the unfolded protein response. Without RtcB, protein stress results in the accumulation of unligated xbp-1 mRNA fragments, defects in the unfolded protein response, and decreased lifespan. RtcB also ligates endogenous pre-tRNA halves, and RtcB mutants have defects in growth and lifespan that can be bypassed by expression of pre-spliced tRNAs. In addition, animals that lack RtcB have defects that are independent of tRNA maturation and the unfolded protein response. Thus, RNA ligation by RtcB is required for the function of multiple endogenous target RNAs including both xbp-1 and tRNAs. RtcB is uniquely capable of performing these ligation functions, and RNA ligation by RtcB mediates multiple essential processes in vivo.
authors.affiliation: Department of Genetics and Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Sara Guckian
authors.initials: SG
authors.lastname: Kosmaczewski
authors.affiliation: Department of Genetics and Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Tyson James
authors.initials: TJ
authors.lastname: Edwards
authors.affiliation: Department of Genetics and Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Sung Min
authors.initials: SM
authors.lastname: Han
authors.affiliation: Department of Cell Biology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Eckwahl
authors.affiliation: Department of Genetics and Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Benjamin Isaiah
authors.initials: BI
authors.lastname: Meyer
authors.affiliation: Biochemistry & Molecular Genetics Department, University of Colorado School of Medicine, Aurora, CO, USA.
authors.forename: Sally
authors.initials: S
authors.lastname: Peach
authors.affiliation: Biochemistry & Molecular Genetics Department, University of Colorado School of Medicine, Aurora, CO, USA.
authors.forename: Jay R
authors.initials: JR
authors.lastname: Hesselberth
authors.affiliation: Department of Cell Biology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Wolin
authors.affiliation: Department of Genetics and Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, CT, USA marc.hammarlund@yale.edu.
authors.forename: Marc
authors.initials: M
authors.lastname: Hammarlund
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics; D011130:RNA Ligase (ATP) / Q000235:genetics / Q000378:metabolism*; D056811:Unfolded Protein Response / Q000235:genetics / Q000502:physiology
chemical_list: D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; C548541:XBP-1 protein, C elegans; D011130:RNA Ligase (ATP)
keywords: Caenorhabditis elegans; HSPC117; RtcB; tRNA; xbp‐1