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Status |
Public on Jan 20, 2017 |
Title |
Pervasive translational regulation of the cell Q1 signalling circuitry underlies mammalian development |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing Other
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Summary |
The degree and dynamics of translational control during mammalian development remain poorly understood. Here we monitored translation of the mammalian genome as cells become specified and organize into tissues in vivo. This identified unexpected and pervasive translational regulation of most of the core signalling circuitry including Shh,Wnt, Hippo, PI3K and MAPK pathways. We further identify and functionally characterize a complex landscape of upstream open reading frames (uORFs) across 5'-untranslated regions (UTRs) of key signalling components. Focusing on the Shh pathway, we demonstrate the importance of uORFs within the major SHH receptor, Ptch1, in control of cell signalling and neuronal differentiation. Finally, we show that the expression of hundreds of mRNAs underlying critical tissue-specific developmental processes is largely regulated at the translation but not transcript levels. Altogether, this work reveals a new layer of translational control to major signalling components and gene regulatory networks that diversifies gene expression spatially across developing tissues.
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Overall design |
Here, we monitored translation of the mammalian genome as cells become specified and organize into tissues in-vivo.
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Contributor(s) |
Fujii K, Shi Z, Zhulyn O, Denans N, Barna M |
Citation(s) |
28195124 |
NIH grant(s) |
Grant ID |
Grant title |
Affiliation |
Name |
R01 HD086634 |
5'UTR RNA Regulons in ribosome-mediated control of embryonic development |
STANFORD UNIVERSITY |
Barna |
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Submission date |
Sep 06, 2016 |
Last update date |
May 15, 2019 |
Contact name |
Zhen Shi |
Organization name |
Stanford
|
Street address |
279 Campus Drive
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City |
Stanford |
State/province |
California |
ZIP/Postal code |
94305 |
Country |
USA |
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Platforms (1) |
GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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Samples (18)
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Relations |
BioProject |
PRJNA342003 |
SRA |
SRP086704 |