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A novel noncoding RNA rescues mutant SOD1‐mediated cell death
Author(s) -
Chang Yueming,
Stockinger Michael P.,
Tashiro Hirofumi,
Glenn Lin Chienliang
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.07-9532com
Subject(s) - sod1 , biology , rna , mutant , ribosome , microbiology and biotechnology , ribosomal rna , polyadenylation , programmed cell death , messenger rna , gene , genetics , apoptosis
Transgenic mice expressing mutant Cu 2+ / Zn 2+ superoxide dismutase SOD1(G93A) develop similar clinical and pathological phenotypes to amyotro‐phic 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 rRNAsequence, 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. FASEB J . 22, 691–702 (2008)