WFRF:(Cargnello M)
Sökning: WFRF:(Cargnello M) > nanoCAGE reveals 5'...
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| Fältnamn | Indikatorer | Metadata |
|---|---|---|
| 000 | 03335naa a2200457 4500 | |
| 001 | oai:prod.swepub.kib.ki.se:133436506 | |
| 003 | SwePub | |
| 008 | 240701s2016 | |||||||||||000 ||eng| | |
| 024 | 7 | a http://kipublications.ki.se/Default.aspx?queryparsed=id:1334365062 URI |
| 024 | 7 | a https://doi.org/10.1101/gr.197566.1152 DOI |
| 040 | a (SwePub)ki | |
| 041 | a engb eng | |
| 042 | 9 SwePub | |
| 072 | 7 | a ref2 swepub-contenttype |
| 072 | 7 | a art2 swepub-publicationtype |
| 100 | 1 | a Gandin, V4 aut |
| 245 | 1 0 | a nanoCAGE reveals 5' UTR features that define specific modes of translation of functionally related MTOR-sensitive mRNAs |
| 264 | c 2016-03-16 | |
| 264 | 1 | b Cold Spring Harbor Laboratory,c 2016 |
| 520 | a The diversity of MTOR-regulated mRNA translation remains unresolved. Whereas ribosome-profiling suggested that MTOR almost exclusively stimulates translation of the TOP (terminal oligopyrimidine motif) and TOP-like mRNAs, polysome-profiling indicated that MTOR also modulates translation of mRNAs without the 5′ TOP motif (non-TOP mRNAs). We demonstrate that in ribosome-profiling studies, detection of MTOR-dependent changes in non-TOP mRNA translation was obscured by low sensitivity and methodology biases. Transcription start site profiling using nano-cap analysis of gene expression (nanoCAGE) revealed that not only do many MTOR-sensitive mRNAs lack the 5′ TOP motif but that 5′ UTR features distinguish two functionally and translationally distinct subsets of MTOR-sensitive mRNAs: (1) mRNAs with short 5′ UTRs enriched for mitochondrial functions, which require EIF4E but are less EIF4A1-sensitive; and (2) long 5′ UTR mRNAs encoding proliferation- and survival-promoting proteins, which are both EIF4E- and EIF4A1-sensitive. Selective inhibition of translation of mRNAs harboring long 5′ UTRs via EIF4A1 suppression leads to sustained expression of proteins involved in respiration but concomitant loss of those protecting mitochondrial structural integrity, resulting in apoptosis. Conversely, simultaneous suppression of translation of both long and short 5′ UTR mRNAs by MTOR inhibitors results in metabolic dormancy and a predominantly cytostatic effect. Thus, 5′ UTR features define different modes of MTOR-sensitive translation of functionally distinct subsets of mRNAs, which may explain the diverse impact of MTOR and EIF4A inhibitors on neoplastic cells. | |
| 700 | 1 | a Masvidal, Lu Karolinska Institutet4 aut |
| 700 | 1 | a Hulea, L4 aut |
| 700 | 1 | a Gravel, SP4 aut |
| 700 | 1 | a Cargnello, M4 aut |
| 700 | 1 | a McLaughlan, S4 aut |
| 700 | 1 | a Cai, YT4 aut |
| 700 | 1 | a Balanathan, P4 aut |
| 700 | 1 | a Morita, M4 aut |
| 700 | 1 | a Rajakumar, A4 aut |
| 700 | 1 | a Furic, L4 aut |
| 700 | 1 | a Pollak, M4 aut |
| 700 | 1 | a Porco, JA4 aut |
| 700 | 1 | a St-Pierre, J4 aut |
| 700 | 1 | a Pelletier, J4 aut |
| 700 | 1 | a Larsson, Ou Karolinska Institutet4 aut |
| 700 | 1 | a Topisirovic, I4 aut |
| 710 | 2 | a Karolinska Institutet4 org |
| 773 | 0 | t Genome researchd : Cold Spring Harbor Laboratoryg 26:5, s. 636-648q 26:5<636-648x 1549-5469x 1088-9051 |
| 856 | 4 | u http://genome.cshlp.org/content/26/5/636.full.pdf |
| 856 | 4 8 | u http://kipublications.ki.se/Default.aspx?queryparsed=id:133436506 |
| 856 | 4 8 | u https://doi.org/10.1101/gr.197566.115 |
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- Gandin, V
- Masvidal, L
- Hulea, L
- Gravel, SP
- Cargnello, M
- McLaughlan, S
- visa fler...
- Cai, YT
- Balanathan, P
- Morita, M
- Rajakumar, A
- Furic, L
- Pollak, M
- Porco, JA
- St-Pierre, J
- Pelletier, J
- Larsson, O
- Topisirovic, I
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