PIWI proteins contribute to apoptosis during the UPR in human airway epithelial cells.
Magdalena GebertSylwia BartoszewskaAnna Janaszak-JasieckaAdrianna MoszyńskaAleksandra CabajJarosław KróliczewskiPiotr MadaneckiRenata J OchockaDavid K CrossmanJames F CollawnRafał BartoszewskiPublished in: Scientific reports (2018)
Small noncoding microRNAs (miRNAs) post-transcriptionally regulate a large portion of the human transcriptome. miRNAs have been shown to play an important role in the unfolded protein response (UPR), a cellular adaptive mechanism that is important in alleviating endoplasmic reticulum (ER) stress and promoting cell recovery. Another class of small noncoding RNAs, the Piwi-interacting RNAs (piRNAs) together with PIWI proteins, was originally shown to play a role as repressors of germline transposable elements. More recent studies, however, indicate that P-element induced WImpy proteins (PIWI proteins) and piRNAs also regulate mRNA levels in somatic tissues. Using genome-wide small RNA next generation sequencing, cell viability assays, and caspase activity assays in human airway epithelial cells, we demonstrate that ER stress specifically up-regulates total piRNA expression profiles, and these changes correlate with UPR-induced apoptosis as shown by up-regulation of two pro-apoptotic factor mRNAs, CHOP and NOXA. Furthermore, siRNA knockdown of PIWIL2 and PIWIL4, two proteins involved in piRNA function, attenuates UPR-related cell death, inhibits piRNA expression, and inhibits the up-regulation of CHOP and NOXA mRNA expression. Hence, we provide evidence that PIWIL2 and PIWIL4 proteins, and potentially the up-regulated piRNAs, constitute a novel epigenetic mechanism that control cellular fate during the UPR.
Keyphrases
- cell death
- induced apoptosis
- endoplasmic reticulum stress
- endothelial cells
- genome wide
- endoplasmic reticulum
- gene expression
- dna methylation
- oxidative stress
- induced pluripotent stem cells
- single cell
- signaling pathway
- copy number
- stem cells
- pluripotent stem cells
- diffuse large b cell lymphoma
- high throughput
- cell cycle arrest
- binding protein
- rna seq
- dna damage
- small molecule
- dna repair
- bone marrow
- cell therapy
- stress induced
- cell free