Selective translational repression of truncated proteins from frameshift mutation-derived mRNAs in tumors.
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-...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2007-05-01
|
| Series: | PLoS Biology |
| Online Access: | https://doi.org/10.1371/journal.pbio.0050109 |
| _version_ | 1819176151643324416 |
|---|---|
| author | Kwon Tae You Long Shan Li Nam-Gyun Kim Hyun Ju Kang Kwi Hye Koh Yong-Joon Chwae Kyoung Mi Kim Yoon Ki Kim Sung Mi Park Sung Key Jang Hoguen Kim |
| author_facet | Kwon Tae You Long Shan Li Nam-Gyun Kim Hyun Ju Kang Kwi Hye Koh Yong-Joon Chwae Kyoung Mi Kim Yoon Ki Kim Sung Mi Park Sung Key Jang Hoguen Kim |
| author_sort | Kwon Tae You |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T21:06:12Z |
| format | Article |
| id | doaj.art-1092f95f3d0347a88e4c4dc0dfec85d7 |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-12-22T21:06:12Z |
| publishDate | 2007-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-1092f95f3d0347a88e4c4dc0dfec85d72022-12-21T18:12:40ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852007-05-0155e10910.1371/journal.pbio.0050109Selective translational repression of truncated proteins from frameshift mutation-derived mRNAs in tumors.Kwon Tae YouLong Shan LiNam-Gyun KimHyun Ju KangKwi Hye KohYong-Joon ChwaeKyoung Mi KimYoon Ki KimSung Mi ParkSung Key JangHoguen KimFrameshift 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.https://doi.org/10.1371/journal.pbio.0050109 |
| spellingShingle | Kwon Tae You Long Shan Li Nam-Gyun Kim Hyun Ju Kang Kwi Hye Koh Yong-Joon Chwae Kyoung Mi Kim Yoon Ki Kim Sung Mi Park Sung Key Jang Hoguen Kim Selective translational repression of truncated proteins from frameshift mutation-derived mRNAs in tumors. PLoS Biology |
| title | Selective translational repression of truncated proteins from frameshift mutation-derived mRNAs in tumors. |
| title_full | Selective translational repression of truncated proteins from frameshift mutation-derived mRNAs in tumors. |
| title_fullStr | Selective translational repression of truncated proteins from frameshift mutation-derived mRNAs in tumors. |
| title_full_unstemmed | Selective translational repression of truncated proteins from frameshift mutation-derived mRNAs in tumors. |
| title_short | Selective translational repression of truncated proteins from frameshift mutation-derived mRNAs in tumors. |
| title_sort | selective translational repression of truncated proteins from frameshift mutation derived mrnas in tumors |
| url | https://doi.org/10.1371/journal.pbio.0050109 |
| work_keys_str_mv | AT kwontaeyou selectivetranslationalrepressionoftruncatedproteinsfromframeshiftmutationderivedmrnasintumors AT longshanli selectivetranslationalrepressionoftruncatedproteinsfromframeshiftmutationderivedmrnasintumors AT namgyunkim selectivetranslationalrepressionoftruncatedproteinsfromframeshiftmutationderivedmrnasintumors AT hyunjukang selectivetranslationalrepressionoftruncatedproteinsfromframeshiftmutationderivedmrnasintumors AT kwihyekoh selectivetranslationalrepressionoftruncatedproteinsfromframeshiftmutationderivedmrnasintumors AT yongjoonchwae selectivetranslationalrepressionoftruncatedproteinsfromframeshiftmutationderivedmrnasintumors AT kyoungmikim selectivetranslationalrepressionoftruncatedproteinsfromframeshiftmutationderivedmrnasintumors AT yoonkikim selectivetranslationalrepressionoftruncatedproteinsfromframeshiftmutationderivedmrnasintumors AT sungmipark selectivetranslationalrepressionoftruncatedproteinsfromframeshiftmutationderivedmrnasintumors AT sungkeyjang selectivetranslationalrepressionoftruncatedproteinsfromframeshiftmutationderivedmrnasintumors AT hoguenkim selectivetranslationalrepressionoftruncatedproteinsfromframeshiftmutationderivedmrnasintumors |