The following is a summary of “Isoform switching regulates the response to ionizing radiation through SRSF1,” published in the March 2024 issue of Oncology by Abdulghani et al.

For a study, researchers aimed to discuss the intricate mechanisms of isoform switching and its impact on the cellular response to ionizing radiation (IR), an area of research that remains relatively understudied despite its profound implications for cancer treatment strategies involving radiotherapy. Through comprehensive analyses, we sought to elucidate alterations in transcript isoform expression following IR exposure and identify the essential proteins orchestrating these changes, emphasizing their potential to modulate radiosensitivity. Leveraging RNA sequencing technology, we meticulously scrutinized B-cell lines derived from 10 healthy individuals multiple times, employing the MISO algorithm to quantify alternative splicing events. 

The investigation extended to the exploration of RNA-binding protein (RBP) motifs within the sequences of IR-responsive isoforms, subsequently validated through RNA-immunoprecipitation, which underscored the Serine/Arginine-Rich Splicing Factor 1 (SRSF1) as a predominant mediator. Notably, the analyses revealed approximately 1,900 radiation-responsive alternatively spliced isoforms, many exhibiting differential expression without concomitant changes in overall gene expression levels. These isoforms demonstrated a propensity for exon skipping or utilization of proximal last exons, with a notable tendency towards shorter transcripts lacking crucial domains implicated in apoptosis inhibition and cell division promotion while retaining those essential for DNA repair processes. Furthermore, the integrated computational, genetic, and molecular analyses unequivocally implicated SRSF1 in mediating radiation-induced isoform-switching events that ultimately facilitate apoptosis. 

Strikingly, exposure to DNA double-strand break-inducing agents corresponded to decreased expression of SRSF1, whereas reduced SRSF1 expression correlated with heightened radiosensitivity both in vitro and among cancer patients. In conclusion, the findings highlight the pivotal role of isoform switching in governing the cellular response to IR and propose SRSF1 as a promising biomarker for evaluating the efficacy of radiotherapy interventions.

Source: sciencedirect.com/science/article/pii/S036030162400333X