A novel noncoding RNA rescues mutant SOD1-mediated cell death.
Transgenic mice expressing mutant Cu2+/Zn2+ superoxide dismutase SOD1(G93A) develop similar clinical and pathological phenotypes to amyotrophic lateral sclerosis (ALS) patients. Here, we utilize representational difference analysis to identify the transcripts that are up-regulated in the presymptomatic stage of SOD1(G93A) mice. Unexpectedly, three predominant clones were 18S or 28S ribosomal RNA (rRNA) segments. One of these clones corresponded to a capped and polyadenylated transcript containing a large portion of 18S rRNA, named MSUR1 (mutant SOD1-up-regulated RNA 1). In vitro expression experiments show that MSUR1 is able to rescue SOD1(G93A)-mediated cell death. Expression of MSUR1 significantly reduces SOD1(G93A)-induced free radical levels and oxidative damage. Further, MSUR1 can reduce hydrogen peroxide-mediated cytotoxicity. MSUR1 does not encode a protein, suggesting its role as a functional noncoding RNA. It is widely expressed in various tissues. Searching the database of GenBank revealed that a large number of expressed sequence tag (EST) clones contain large portions of rRNA sequence, potentially indicating a heretofore overlooked class of mRNAs with functional significance.
Chang
Yueming
Y
The Ohio State University, Department of Neuroscience, 333 W. 10th Ave., Columbus, Ohio 43210, USA.
Stockinger
Michael P
MP
Tashiro
Hirofumi
H
Lin
Chien-liang Glenn
CL
D019943:Amino Acid Substitution; D000818:Animals; D001483:Base Sequence; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009154:Mutation; D012335:RNA, Ribosomal / Q000378:metabolism; D022661:RNA, Untranslated / Q000493:pharmacokinetics / Q000502:physiology*; D013482:Superoxide Dismutase / Q000235:genetics* / Q000502:physiology; D000072105:Superoxide Dismutase-1; D015854:Up-Regulation
D012335:RNA, Ribosomal; D022661:RNA, Untranslated; C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1