mTOR phosphorylates IMP2 to promote IGF2 mRNA translation by internal ribosomal entry
Variants in the IMP2 (insulin-like growth factor 2 [IGF2] mRNA-binding protein 2) gene are implicated in susceptibility to type 2 diabetes. We describe the ability of mammalian target of rapamycin (mTOR) to regulate the cap-independent translation of IGF2 mRNA through phosphorylation of IMP2, an onc...
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| Format: | Article |
| Language: | en_US |
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Cold Spring Harbor Laboratory Press
2014
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| Online Access: | http://hdl.handle.net/1721.1/88501 |
| _version_ | 1826201503872843776 |
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| author | Dai, Ning Rapley, Joseph Angel, Matthew Yanik, Mehmet Fatih Blower, Michael D. Avruch, Joseph |
| author2 | Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science |
| author_facet | Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Dai, Ning Rapley, Joseph Angel, Matthew Yanik, Mehmet Fatih Blower, Michael D. Avruch, Joseph |
| author_sort | Dai, Ning |
| collection | MIT |
| description | Variants in the IMP2 (insulin-like growth factor 2 [IGF2] mRNA-binding protein 2) gene are implicated in susceptibility to type 2 diabetes. We describe the ability of mammalian target of rapamycin (mTOR) to regulate the cap-independent translation of IGF2 mRNA through phosphorylation of IMP2, an oncofetal RNA-binding protein. IMP2 is doubly phosphorylated in a rapamycin-inhibitable, amino acid-dependent manner in cells and by mTOR in vitro. Double phosphorylation promotes IMP2 binding to the IGF2 leader 3 mRNA 5′ untranslated region, and the translational initiation of this mRNA through eIF-4E- and 5′ cap-independent internal ribosomal entry. Unexpectedly, the interaction of IMP2 with mTOR complex 1 occurs through mTOR itself rather than through raptor. Whereas depletion of mTOR strongly inhibits IMP2 phosphorylation in cells, comparable depletion of raptor has no effect; moreover, the ability of mTOR to phosphorylate IMP2 in vitro is unaffected by the elimination of raptor. Dual phosphorylation of IMP2 at the mTOR sites is evident in the mouse embryo, likely coupling nutrient sufficiency to IGF2 expression and fetal growth. Doubly phosphorylated IMP2 is also widely expressed in adult tissues, including islets of Langerhans. |
| first_indexed | 2024-09-23T11:52:28Z |
| format | Article |
| id | mit-1721.1/88501 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:52:28Z |
| publishDate | 2014 |
| publisher | Cold Spring Harbor Laboratory Press |
| record_format | dspace |
| spelling | mit-1721.1/885012022-10-01T06:38:09Z mTOR phosphorylates IMP2 to promote IGF2 mRNA translation by internal ribosomal entry Dai, Ning Rapley, Joseph Angel, Matthew Yanik, Mehmet Fatih Blower, Michael D. Avruch, Joseph Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Angel, Matthew Yanik, Mehmet Fatih Variants in the IMP2 (insulin-like growth factor 2 [IGF2] mRNA-binding protein 2) gene are implicated in susceptibility to type 2 diabetes. We describe the ability of mammalian target of rapamycin (mTOR) to regulate the cap-independent translation of IGF2 mRNA through phosphorylation of IMP2, an oncofetal RNA-binding protein. IMP2 is doubly phosphorylated in a rapamycin-inhibitable, amino acid-dependent manner in cells and by mTOR in vitro. Double phosphorylation promotes IMP2 binding to the IGF2 leader 3 mRNA 5′ untranslated region, and the translational initiation of this mRNA through eIF-4E- and 5′ cap-independent internal ribosomal entry. Unexpectedly, the interaction of IMP2 with mTOR complex 1 occurs through mTOR itself rather than through raptor. Whereas depletion of mTOR strongly inhibits IMP2 phosphorylation in cells, comparable depletion of raptor has no effect; moreover, the ability of mTOR to phosphorylate IMP2 in vitro is unaffected by the elimination of raptor. Dual phosphorylation of IMP2 at the mTOR sites is evident in the mouse embryo, likely coupling nutrient sufficiency to IGF2 expression and fetal growth. Doubly phosphorylated IMP2 is also widely expressed in adult tissues, including islets of Langerhans. National Institutes of Health (U.S.) (NIH grant CA73818) National Institutes of Health (U.S.) (NIH grant DK17776) National Institutes of Health (U.S.) (NIH grant DK057521) United States. American Recovery and Reinvestment Act of 2009 2014-07-25T17:08:02Z 2014-07-25T17:08:02Z 2011-05 2011-04 Article http://purl.org/eprint/type/JournalArticle 0890-9369 http://hdl.handle.net/1721.1/88501 Dai, N., J. Rapley, M. Angel, M. F. Yanik, M. D. Blower, and J. Avruch. “mTOR Phosphorylates IMP2 to Promote IGF2 mRNA Translation by Internal Ribosomal Entry.” Genes & Development 25, no. 11 (June 1, 2011): 1159–1172. en_US http://dx.doi.org/10.1101/gad.2042311 Genes & Development Article is available under a Creative Commons license; see publisher’s site for details. http://creativecommons.org/ application/pdf Cold Spring Harbor Laboratory Press Cold Spring Harbor Laboratory Press |
| spellingShingle | Dai, Ning Rapley, Joseph Angel, Matthew Yanik, Mehmet Fatih Blower, Michael D. Avruch, Joseph mTOR phosphorylates IMP2 to promote IGF2 mRNA translation by internal ribosomal entry |
| title | mTOR phosphorylates IMP2 to promote IGF2 mRNA translation by internal ribosomal entry |
| title_full | mTOR phosphorylates IMP2 to promote IGF2 mRNA translation by internal ribosomal entry |
| title_fullStr | mTOR phosphorylates IMP2 to promote IGF2 mRNA translation by internal ribosomal entry |
| title_full_unstemmed | mTOR phosphorylates IMP2 to promote IGF2 mRNA translation by internal ribosomal entry |
| title_short | mTOR phosphorylates IMP2 to promote IGF2 mRNA translation by internal ribosomal entry |
| title_sort | mtor phosphorylates imp2 to promote igf2 mrna translation by internal ribosomal entry |
| url | http://hdl.handle.net/1721.1/88501 |
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