 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Jul 31, 2014 |
| Title |
LARP1 mRNP scaffolds mTORC1 to stimulate translation initiation of an essential class of mRNAs |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Other
|
| Summary |
The RNA biding protein, LARP1, has been proposed to function downstream of mTORC1 to positively regulate the translation of 5’TOP mRNAs such as ribosome protein (RP) mRNAs. However, its regulatory roles in mTORC1-mediated translation remain unclear. PAR-CLIP of LARP1 revealed its direct and dynamic interactions with RP mRNAs through pyrimidine-enriched sequences in the 5’UTR of RP mRNAs when mTOR activity is inhibited. Importantly, this LARP1 is a direct substrate of mTORC1 and S6K1/Akt, and phosphorylated LARP1 scaffolds mTORC1 on translation-competent mRNAs to facilitate 4EBP1 and S6K1 phosphorylation. Ablation of LARP1 causes multiple defects in the processes of translation including abnormal eIF4G1 interaction with RP mRNAs and inefficient RP mRNA elongation thereby reducing ribosome biogenesis and cell proliferation. These observations illustrate that LARP1 functions both an effector and a regulator for local mTORC1 activity, and acts as a molecular switch for ribosome biogenesis by sensing growth factor/nutrient signaling.
|
| |
|
| Overall design |
LARP1-bound RNA regions were sequenced from HEK293T cells under growing or mTOR-inactive conditions. In parallel, mRNA abundance was quantified, in biological duplicate, from HEK293T cells under the same conditions. Sequencing reads were mapped to human transcriptome reference from hg19 to determine LARP1 binding sites and mRNA abundances.
|
| |
|
| Contributor(s) |
Hong S, Freeberg MA, Avani K, Ting H, Yao Y, Tomoko F, Andy K, Tsukasa S, Kim JK, Inoki K |
| Citation(s) |
28650797 |
| |
| Submission date |
Jul 18, 2014 |
| Last update date |
Jul 11, 2019 |
| Contact name |
Mallory Ann Freeberg |
| E-mail(s) |
mfreebe2@jhu.edu
|
| Organization name |
Johns Hopkins University
|
| Department |
Department of Biology
|
| Street address |
3400 N Charles St
|
| City |
Baltimore |
| State/province |
MD |
| ZIP/Postal code |
21211 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (6)
|
|
| Relations |
| BioProject |
PRJNA255679 |
| SRA |
SRP044653 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE59599_RAW.tar |
180.0 Kb |
(http)(custom) |
TAR (of TXT) |
| GSE59599_mRNAseq_gene_RPKM.txt.gz |
1.5 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
| Processed data provided as supplementary file |
|
|
|
|
 |
Less...
More...