Identification of alternatively spliced GRIM-19 mRNA in kidney cancer tissues.
Gene associated with Retinoid-Interferon-induced Mortality (GRIM)-19 was originally identified as a regulatory gene necessary for interferon-beta and retinoic acid-induced cell death. Further studies revealed that GRIM-19 is a subunit of mitochondrial respiratory chain complex I. Previous studies show that the expression of GRIM-19 is lost or severely depressed in a number of primary renal cell carcinomas (RCCs) and in some urinogenital tumors. Four point mutations were found in the GRIM-19 gene in mitochondria-rich (Hürthle) tumors and one point mutation was reported in RCC. In this study, we report an alternatively splicing form of GRIM-19 mRNA with intron 3 by reverse transcriptase PCR. This splicing variant is found in kidney tumor tissues but not in matched normal tissues. Furthermore, we found that in addition to GRIM-19, the protein level of NDUFS3, which is another mitochondrial complex I subunit, was also diminished in kidney tumor tissues when compared with paired normal tissues. Our finding suggested that the alternative splicing form of GRIM-19 is tumor tissue specific.
He
Xuelian
X
Signal Transduction Laboratory, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore.
Cao
Xinmin
X
D000293:Adolescent; D000328:Adult; D000368:Aged; D017398:Alternative Splicing; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D001483:Base Sequence; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D015536:Down-Regulation; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007438:Introns / Q000235:genetics; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008928:Mitochondria; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D051017:Apoptosis Regulatory Proteins; D012333:RNA, Messenger; D009247:NADH, NADPH Oxidoreductases; C439057:NDUFA13 protein, human