AI Article Synopsis
- mTOR is crucial for promoting cell growth and protein synthesis by enhancing mRNA translation through regulating specific proteins like eIF4E.
- Researchers conducted a proteomic screen to identify proteins associated with the mRNA 5' cap, discovering LARP1 as a key player in mTOR-dependent translation.
- LARP1 facilitates the translation of specific mRNAs tied to the translational machinery and is essential for overall protein synthesis, cell growth, and proliferation, highlighting its significant regulatory role.
Article Abstract
The mammalian target of rapamycin (mTOR) promotes cell growth and proliferation by promoting mRNA translation and increasing the protein synthetic capacity of the cell. Although mTOR globally promotes translation by regulating the mRNA 5' cap-binding protein eIF4E (eukaryotic initiation factor 4E), it also preferentially regulates the translation of certain classes of mRNA via unclear mechanisms. To help fill this gap in knowledge, we performed a quantitative proteomic screen to identify proteins that associate with the mRNA 5' cap in an mTOR-dependent manner. Using this approach, we identified many potential regulatory factors, including the putative RNA-binding protein LARP1 (La-related protein 1). Our results indicate that LARP1 associates with actively translating ribosomes via PABP and that LARP1 stimulates the translation of mRNAs containing a 5' terminal oligopyrimidine (TOP) motif, encoding for components of the translational machinery. We found that LARP1 associates with the mTOR complex 1 (mTORC1) and is required for global protein synthesis as well as cell growth and proliferation. Together, these data reveal important molecular mechanisms involved in TOP mRNA translation and implicate LARP1 as an important regulator of cell growth and proliferation.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3937514 | PMC |
| http://dx.doi.org/10.1101/gad.231407.113 | DOI Listing |
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