Uncovering the Localization and Function of a Novel Read-Through Transcript ' TOMM40-APOE '.
Shichen ChangSatoru ToriiJun InamoKinya IshikawaYuta KochiShigeomi ShimizuPublished in: Cells (2023)
Recent advancements in genome analysis technology have revealed the presence of read-through transcripts in which transcription continues by skipping the polyA signal. We here identified and characterized a new read-through transcript, TOMM40-APOE . With cDNA amplification from THP-1 cells, the TOMM40-APOE3 product was successfully generated. We also generated TOMM40-APOE4 , another isoform, by introducing point mutations. Notably, while APOE3 and APOE4 exhibited extracellular secretion, both TOMM40-APOE3 and TOMM40-APOE4 were localized exclusively to the mitochondria. But functionally, they did not affect mitochondrial membrane potential. Cell death induction studies illustrated increased cell death with TOMM40-APOE3 and TOMM40-APOE4, and we did not find any difference in cellular function between the two isoforms. These findings indicated that the new mitochondrial protein TOMM40-APOE has cell toxic ability.
Keyphrases
- cognitive decline
- high fat diet
- cell death
- mild cognitive impairment
- single cell
- oxidative stress
- single molecule
- type diabetes
- adipose tissue
- cell cycle arrest
- rna seq
- induced apoptosis
- mesenchymal stem cells
- risk assessment
- small molecule
- climate change
- endoplasmic reticulum stress
- reactive oxygen species
- dna methylation