The 40<i>S</i>-LARP1 complex reprograms the cellular translatome upon mTOR inhibition to preserve the protein synthetic capacity.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34818049.
- Also identified by DOI 10.1126/sciadv.abg9275 and PMC identifier 8612684.
- Licence recorded as CC BY-NC.
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Abstract
Ribosomes execute the transcriptional program in every cell. Critical to sustain nearly all cellular activities, ribosome biogenesis requires the translation of ~200 factors of which 80 are ribosomal proteins (RPs). As ribosome synthesis depends on RP mRNA translation, a priority within the translatome architecture should exist to ensure the preservation of ribosome biogenesis capacity, particularly under adverse growth conditions. Here, we show that under critical metabolic constraints characterized by mTOR inhibition, LARP1 complexed with the 40<i>S</i> subunit protects from ribophagy the mRNAs regulon for ribosome biogenesis and protein synthesis, acutely preparing the translatome to promptly resume ribosomes production after growth conditions return permissive. Characterizing the LARP1-protected translatome revealed a set of 5′TOP transcript isoforms other than RPs involved in energy production and in mitochondrial function, among other processes, indicating that the mTOR-LARP1-5′TOP axis acts at the translational level as a primary guardian of the cellular anabolic capacity.