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A novel noncoding RNA rescues mutant SOD1-mediated cell death

Yueming Chang^*,, Michael P. Stockinger^*, Hirofumi Tashiro^* and Chien-liang Glenn Lin^*,,1

^* Department of Neuroscience,

Ohio State Biochemistry Program, The Ohio State University, Columbus, Ohio, USA

¹Correspondence: The Ohio State University, Department of Neuroscience, 4198 Graves Hall, 333 W. 10th Ave., Columbus, Ohio 43210, USA. E-mail: lin.492{at}osu.edu

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, Y., Stockinger, M. P., Tashiro, H., Glenn Lin, C. A novel noncoding RNA rescues mutant SOD1-mediated cell death.

Key Words: ALS • neurodegeneration • rRNA