Nitric oxide activation of Erk1/2 regulates the stability and translation of mRNA transcripts containing CU-rich elements
Nitric oxide (NO•) can stabilize mRNA by activating p38 mitogen-activated protein kinase (MAPK). Here, transcript stabilization by NO• was investigated in human THP-1 cells using microarrays. After LPS pre-stimulation, cells were treated with actinomycin D and then exposed to NO• without or with the...
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| Format: | Online |
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Oxford University Press
2006
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1475749/ |
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pubmed-14757492006-06-26 Nitric oxide activation of Erk1/2 regulates the stability and translation of mRNA transcripts containing CU-rich elements Wang, Shuibang Zhang, Jianhua Theel, Stephanie Barb, Jennifer J. Munson, Peter J. Danner, Robert L. Article Nitric oxide (NO•) can stabilize mRNA by activating p38 mitogen-activated protein kinase (MAPK). Here, transcript stabilization by NO• was investigated in human THP-1 cells using microarrays. After LPS pre-stimulation, cells were treated with actinomycin D and then exposed to NO• without or with the p38 MAPK inhibitor SB202190 (SB). The decay of 220 mRNAs was affected; most were stabilized by NO•. Unexpectedly, SB often enhanced rather than antagonized transcript stability. NO• activated p38 MAPK and Erk1/2; SB blocked p38 MAPK, but further activated Erk1/2. RT–PCR confirmed that NO• and SB could additively stabilize certain mRNA transcripts, an effect abolished by Erk1/2 inhibition. In affected genes, these responses were associated with CU-rich elements (CURE) in 3′-untranslated regions (3′-UTR). NO• stabilized the mRNA of a CURE-containing reporter gene, while repressing translation. Dominant-negative Mek1, an Erk1/2 inhibitor, abolished this effect. NO• similarly stabilized, but blocked translation of MAP3K7IP2, a natural CURE-containing gene. NO• increased hnRNP translocation to the cytoplasm and binding to CURE. Over-expression of hnRNP K, like NO•, repressed translation of CURE-containing mRNA. These findings define a sequence-specific mechanism of NO•-triggered gene regulation that stabilizes mRNA, but represses translation. Oxford University Press 2006 2006-06-06 /pmc/articles/PMC1475749/ /pubmed/16757573 http://dx.doi.org/10.1093/nar/gkl386 Text en © 2006 The Author(s) |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Wang, Shuibang Zhang, Jianhua Theel, Stephanie Barb, Jennifer J. Munson, Peter J. Danner, Robert L. |
| spellingShingle |
Wang, Shuibang Zhang, Jianhua Theel, Stephanie Barb, Jennifer J. Munson, Peter J. Danner, Robert L. Nitric oxide activation of Erk1/2 regulates the stability and translation of mRNA transcripts containing CU-rich elements |
| author_facet |
Wang, Shuibang Zhang, Jianhua Theel, Stephanie Barb, Jennifer J. Munson, Peter J. Danner, Robert L. |
| author_sort |
Wang, Shuibang |
| title |
Nitric oxide activation of Erk1/2 regulates the stability and translation of mRNA transcripts containing CU-rich elements |
| title_short |
Nitric oxide activation of Erk1/2 regulates the stability and translation of mRNA transcripts containing CU-rich elements |
| title_full |
Nitric oxide activation of Erk1/2 regulates the stability and translation of mRNA transcripts containing CU-rich elements |
| title_fullStr |
Nitric oxide activation of Erk1/2 regulates the stability and translation of mRNA transcripts containing CU-rich elements |
| title_full_unstemmed |
Nitric oxide activation of Erk1/2 regulates the stability and translation of mRNA transcripts containing CU-rich elements |
| title_sort |
nitric oxide activation of erk1/2 regulates the stability and translation of mrna transcripts containing cu-rich elements |
| description |
Nitric oxide (NO•) can stabilize mRNA by activating p38 mitogen-activated protein kinase (MAPK). Here, transcript stabilization by NO• was investigated in human THP-1 cells using microarrays. After LPS pre-stimulation, cells were treated with actinomycin D and then exposed to NO• without or with the p38 MAPK inhibitor SB202190 (SB). The decay of 220 mRNAs was affected; most were stabilized by NO•. Unexpectedly, SB often enhanced rather than antagonized transcript stability. NO• activated p38 MAPK and Erk1/2; SB blocked p38 MAPK, but further activated Erk1/2. RT–PCR confirmed that NO• and SB could additively stabilize certain mRNA transcripts, an effect abolished by Erk1/2 inhibition. In affected genes, these responses were associated with CU-rich elements (CURE) in 3′-untranslated regions (3′-UTR). NO• stabilized the mRNA of a CURE-containing reporter gene, while repressing translation. Dominant-negative Mek1, an Erk1/2 inhibitor, abolished this effect. NO• similarly stabilized, but blocked translation of MAP3K7IP2, a natural CURE-containing gene. NO• increased hnRNP translocation to the cytoplasm and binding to CURE. Over-expression of hnRNP K, like NO•, repressed translation of CURE-containing mRNA. These findings define a sequence-specific mechanism of NO•-triggered gene regulation that stabilizes mRNA, but represses translation. |
| publisher |
Oxford University Press |
| publishDate |
2006 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1475749/ |
| _version_ |
1611383974230228992 |