2'-O-methylation of the mRNA cap protects RNAs from decapping and degradation by DXO.
The 5' RNA cap structure (m7GpppRNA) is a key feature of eukaryotic mRNAs with important roles in stability, splicing, polyadenylation, mRNA export, and translation. Higher eukaryotes can further modify this minimal cap structure with the addition of a methyl group on the ribose 2'-O posit...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5877831?pdf=render |
| _version_ | 1818328930150514688 |
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| author | Frédéric Picard-Jean Carolin Brand Maude Tremblay-Létourneau Andréa Allaire Maxime C Beaudoin Simon Boudreault Cyntia Duval Julien Rainville-Sirois Francis Robert Jerry Pelletier Brian J Geiss Martin Bisaillon |
| author_facet | Frédéric Picard-Jean Carolin Brand Maude Tremblay-Létourneau Andréa Allaire Maxime C Beaudoin Simon Boudreault Cyntia Duval Julien Rainville-Sirois Francis Robert Jerry Pelletier Brian J Geiss Martin Bisaillon |
| author_sort | Frédéric Picard-Jean |
| collection | DOAJ |
| description | The 5' RNA cap structure (m7GpppRNA) is a key feature of eukaryotic mRNAs with important roles in stability, splicing, polyadenylation, mRNA export, and translation. Higher eukaryotes can further modify this minimal cap structure with the addition of a methyl group on the ribose 2'-O position of the first transcribed nucleotide (m7GpppNmpRNA) and sometimes on the adjoining nucleotide (m7GpppNmpNmpRNA). In higher eukaryotes, the DXO protein was previously shown to be responsible for both decapping and degradation of RNA transcripts harboring aberrant 5' ends such as pRNA, pppRNA, GpppRNA, and surprisingly, m7GpppRNA. It was proposed that the interaction of the cap binding complex with the methylated cap would prevent degradation of m7GpppRNAs by DXO. However, the critical role of the 2'-O-methylation found in higher eukaryotic cap structures was not previously addressed. In the present study, we demonstrate that DXO possesses both decapping and exoribonuclease activities toward incompletely capped RNAs, only sparing RNAs with a 2'-O-methylated cap structure. Fluorescence spectroscopy assays also revealed that the presence of the 2'-O-methylation on the cap structure drastically reduces the affinity of DXO for RNA. Moreover, immunofluorescence and structure-function assays also revealed that a nuclear localisation signal is located in the amino-terminus region of DXO. Overall, these results are consistent with a quality control mechanism in which DXO degrades incompletely capped RNAs. |
| first_indexed | 2024-12-13T12:39:59Z |
| format | Article |
| id | doaj.art-ef263c70fce2423fbcaa628572258e52 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T12:39:59Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-ef263c70fce2423fbcaa628572258e522022-12-21T23:45:41ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01133e019380410.1371/journal.pone.01938042'-O-methylation of the mRNA cap protects RNAs from decapping and degradation by DXO.Frédéric Picard-JeanCarolin BrandMaude Tremblay-LétourneauAndréa AllaireMaxime C BeaudoinSimon BoudreaultCyntia DuvalJulien Rainville-SiroisFrancis RobertJerry PelletierBrian J GeissMartin BisaillonThe 5' RNA cap structure (m7GpppRNA) is a key feature of eukaryotic mRNAs with important roles in stability, splicing, polyadenylation, mRNA export, and translation. Higher eukaryotes can further modify this minimal cap structure with the addition of a methyl group on the ribose 2'-O position of the first transcribed nucleotide (m7GpppNmpRNA) and sometimes on the adjoining nucleotide (m7GpppNmpNmpRNA). In higher eukaryotes, the DXO protein was previously shown to be responsible for both decapping and degradation of RNA transcripts harboring aberrant 5' ends such as pRNA, pppRNA, GpppRNA, and surprisingly, m7GpppRNA. It was proposed that the interaction of the cap binding complex with the methylated cap would prevent degradation of m7GpppRNAs by DXO. However, the critical role of the 2'-O-methylation found in higher eukaryotic cap structures was not previously addressed. In the present study, we demonstrate that DXO possesses both decapping and exoribonuclease activities toward incompletely capped RNAs, only sparing RNAs with a 2'-O-methylated cap structure. Fluorescence spectroscopy assays also revealed that the presence of the 2'-O-methylation on the cap structure drastically reduces the affinity of DXO for RNA. Moreover, immunofluorescence and structure-function assays also revealed that a nuclear localisation signal is located in the amino-terminus region of DXO. Overall, these results are consistent with a quality control mechanism in which DXO degrades incompletely capped RNAs.http://europepmc.org/articles/PMC5877831?pdf=render |
| spellingShingle | Frédéric Picard-Jean Carolin Brand Maude Tremblay-Létourneau Andréa Allaire Maxime C Beaudoin Simon Boudreault Cyntia Duval Julien Rainville-Sirois Francis Robert Jerry Pelletier Brian J Geiss Martin Bisaillon 2'-O-methylation of the mRNA cap protects RNAs from decapping and degradation by DXO. PLoS ONE |
| title | 2'-O-methylation of the mRNA cap protects RNAs from decapping and degradation by DXO. |
| title_full | 2'-O-methylation of the mRNA cap protects RNAs from decapping and degradation by DXO. |
| title_fullStr | 2'-O-methylation of the mRNA cap protects RNAs from decapping and degradation by DXO. |
| title_full_unstemmed | 2'-O-methylation of the mRNA cap protects RNAs from decapping and degradation by DXO. |
| title_short | 2'-O-methylation of the mRNA cap protects RNAs from decapping and degradation by DXO. |
| title_sort | 2 o methylation of the mrna cap protects rnas from decapping and degradation by dxo |
| url | http://europepmc.org/articles/PMC5877831?pdf=render |
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