RNA repair: an antidote to cytotoxic eukaryal RNA damage.
RNA healing and sealing enzymes drive informational and stress response pathways entailing repair of programmed 2',3' cyclic PO(4)/5'-OH breaks. Fungal, plant, and phage tRNA ligases use different strategies to discriminate the purposefully broken ends of the anticodon loop. Whereas phage ligase recognizes the tRNA fold, yeast and plant ligases do not and are instead hardwired to seal only the tRNA 3'-OH, 2'-PO(4) ends formed by healing of a cyclic phosphate. tRNA anticodon damage inflicted by secreted ribotoxins such as fungal gamma-toxin underlies a rudimentary innate immune system. Yeast cells are susceptible to gamma-toxin because the sealing domain of yeast tRNA ligase is unable to rectify a break at the modified wobble base of tRNA(Glu(UUC)). Plant andphage tRNA repair enzymes protect yeast from gamma-toxin because they are able to reverse the damage. Our studies underscore how a ribotoxin exploits an Achilles' heel in the target cell's tRNA repair system.
Nandakumar
Jayakrishnan
J
Molecular Biology Program, Sloan-Kettering Institute, New York, NY 10065, USA.
Schwer
Beate
B
Schaffrath
Raffael
R
Shuman
Stewart
S
D000931:Antidotes / Q000378:metabolism*; D017360:Arabidopsis / Q000378:metabolism; D029681:Arabidopsis Proteins / Q000378:metabolism; D001435:Bacteriophages / Q000201:enzymology; D001483:Base Sequence; D016923:Cell Death / Q000187:drug effects; D005057:Eukaryotic Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D055646:Killer Factors, Yeast; D008969:Molecular Sequence Data; D009183:Mycotoxins / Q000633:toxicity; D009690:Nucleic Acid Conformation / Q000187:drug effects; D011130:RNA Ligase (ATP) / Q000378:metabolism; D012331:RNA, Fungal / Q000378:metabolism; D012343:RNA, Transfer / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012352:RNA, Transfer, Glu / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D013379:Substrate Specificity / Q000187:drug effects; D014118:Toxins, Biological / Q000633:toxicity
D000931:Antidotes; D029681:Arabidopsis Proteins; D055646:Killer Factors, Yeast; D009183:Mycotoxins; D012331:RNA, Fungal; D012352:RNA, Transfer, Glu; D029701:Saccharomyces cerevisiae Proteins; D014118:Toxins, Biological; C058975:zymocin; D012343:RNA, Transfer; D011130:RNA Ligase (ATP); C507673:Trl1 protein, S cerevisiae