Omics · study · 2026
Lsp2 links mTORC1 to TOP mRNA translation and lifespan in Drosophila
Listed in NCBI GEO
Mechanistic target of rapamycin complex 1 (mTORC1) senses nutrient availability to orchestrate metabolic processes critical for physiological homeostasis and organismal aging 1.
Description
While mTORC1 preferentially regulates the translation of 5′-terminal oligopyrimidine (TOP) motif-containing mRNAs that predominantly encode ribosomal proteins (RPs) via the translational repressor 4E-BP 2, this mTORC1 function is resistant to rapamycin inhibition 3.
TOP mRNAs are exceptionally abundant, thus imposing a major translational burden on cells; yet how their translation is physiologically tuned and linked to longevity remain unexplored. Here we identify Lsp2, originally known as a storage protein 4, as an adipose effector and feedback activator of mTORC1 that modulates lifespan in Drosophila. Lsp2 expression is induced by essential amino acids (EAAs) via mTORC1 and gated by additional signals of nutrient sufficiency.
Read the rest (2 more)
Genetic ablation of Lsp2 robustly extends lifespan without impairing key life-history traits such as reproduction. Translatomic profiling shows that loss of Lsp2 selectively reduces global TOP mRNA translation in a 4E-BP–dependent manner, thereby extending lifespan via a mechanism distinct from rapamycin. Evolutionarily, TOP motifs co-emerged with 4E-BP and are present in nearly all Drosophila RP mRNAs.
Moreover, we demonstrate that their role in translational control extends to Drosophila. Collectively, our findings reveal a nutrient-induced physiological factor that amplifies mTORC1 output in TOP mRNA translation and regulates organismal longevity.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE295nnn/GSE295794 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE295794 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1256379 ncbi.nlm.nih.gov/bioproject/PRJNA1256379 ↗
project · from NCBI GEO
Topics
- Stated by source
- Drosophila melanogaster · Expression profiling by high throughput sequencing
- From keywords
- Life Sciences
- Inferred from text
- Biochemistry and cell biology 70%
Related
- Possibly the same asLsp2 links mTORC1 to TOP mRNA translation and lifespan in Drosophila
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE295794 | 13 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[field].anzsrc:group:3101 | enrichment · NCBI GEO | taxonomy-embedding@1.1.0 | title+keywords+description (70%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:7227 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |