Project description:Alternative RNA 3’-end processing provides an important source of transcriptome diversification, which impacts various biological processes and the etiology of diseases, including cancer. A prime example of this is the transcript isoform switch that leads to the read-through expression of the long non-coding RNA NEAT1_2, at the expense of the shorter polyadenylated transcript NEAT1_1. Expression of NEAT1_2 is required for the formation of paraspeckles (PS), nuclear bodies that protect cancer cells from oncogene-induced replication stress and chemotherapy. Searching for proteins that modulate this isoform switching event we identified factors involved in the 3’-end processing of polyadenylated (pA+) RNA as well as several components of the Integrator complex. Perturbation experiments established that, by promoting the cleavage of NEAT1_2, Integrator forces NEAT1_2 to NEAT1_1 isoform switching and, thereby, restrains PS assembly. Consistently, low expression levels of several Integrator subunits correlated with poorer prognosis of cancer patients exposed to chemotherapeutics. Our study identifies Integrator as a key regulator of PS biogenesis and establish a link between Integrator, cancer biology and chemosensitivity, which may be exploited therapeutically.

2020-08-21 | GSE148755 | GEO

The small molecule Retro-1 enhances the pharmacological actions of antisense and splice switching oligonucleotides.

Project description: Not available

| S-EPMC3616695 | biostudies-literature

Open reading frame correction using splice-switching antisense oligonucleotides for the treatment of cystic fibrosis.

Project description: Not available

| S-EPMC8784102 | biostudies-literature

Splice-Switching Antisense Oligonucleotides as a Targeted Intrinsic Engineering Tool for Generating Armored Redirected T Cells.

Project description: Not available

| S-EPMC7997720 | biostudies-literature