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Selective translational repression of truncated proteins from frameshift mutation-derived mRNAs in tumors

Authors
 Kwon Tae You  ;  Long Shan Li  ;  Hoguen Kim  ;  Sung Key Jang  ;  Sung Mi Park  ;  Yoon Ki Kim  ;  Kyoung Mi Kim  ;  Yong-Joon Chwae  ;  Kwi Hye Koh  ;  Hyun Ju Kang  ;  Nam-Gyun Kim 
Citation
 PLOS COMPUTATIONAL BIOLOGY, Vol.5(5) : e1098, 2007 
Journal Title
PLOS COMPUTATIONAL BIOLOGY
ISSN
 1553-734X 
Issue Date
2007
Abstract
Frameshift and nonsense mutations are common in tumors with microsatellite instability, and mRNAs from these mutated genes have premature termination codons (PTCs). Abnormal mRNAs containing PTCs are normally degraded by the nonsense-mediated mRNA decay (NMD) system. However, PTCs located within 50–55 nucleotides of the last exon–exon junction are not recognized by NMD (NMD-irrelevant), and some PTC-containing mRNAs can escape from the NMD system (NMD-escape). We investigated protein expression from NMD-irrelevant and NMD-escape PTC-containing mRNAs by Western blotting and transfection assays. We demonstrated that transfection of NMD-irrelevant PTC-containing genomic DNA of MARCKS generates truncated protein. In contrast, NMD-escape PTC-containing versions of hMSH3 and TGFBR2 generate normal levels of mRNA, but do not generate detectable levels of protein. Transfection of NMD-escape mutant TGFBR2 genomic DNA failed to generate expression of truncated proteins, whereas transfection of wild-type TGFBR2 genomic DNA or mutant PTC-containing TGFBR2 cDNA generated expression of wild-type protein and truncated protein, respectively. Our findings suggest a novel mechanism of gene expression regulation for PTC-containing mRNAs in which the deleterious transcripts are regulated either by NMD or translational repression.
Files in This Item:
T200700265.pdf Download
DOI
10.1371/journal.pbio.0050109
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kang, Hyun Ju(강현주)
Koh, Kwi Hye(고귀혜)
Kim, Nam Gyun(김남균)
Kim, Hogeun(김호근)
You, Kwon Tae(유권태)
Li, Long Shan(이용산)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/97310
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