Crosstalk between alternative splicing and inflammatory bowel disease: Basic mechanisms, biotechnological progresses and future perspectives

Abstract

BackgroundAlternative splicing (AS) is an omnipresent regulatory mechanism of gene expression that enables the generation of diverse splice isoforms from a single gene. Recently, AS events have gained considerable momentum in the pathogenesis of inflammatory bowel disease (IBD).MethodsOur review has summarized the complex process of RNA splicing, and firstly highlighted the potential involved molecules that target aberrant splicing events in IBD. The quantitative transcriptome analyses such as microarrays, next‐generation sequencing (NGS) for AS events in IBD have been also discussed.ResultsAvailable evidence suggests that some abnormal splicing RNAs can lead to multiple intestinal disorders during the onset of IBD as well as the progression to colitis‐associated cancer (CAC), including gut microbiota perturbations, intestinal barrier dysfunctions, innate/adaptive immune dysregulations, pro‐fibrosis activation and some other risk factors. Moreover, current data show that the advanced technologies, including microarrays and NGS, have been pioneeringly employed to screen the AS candidates and elucidate the potential regulatory mechanisms of IBD. Besides, other biotechnological progresses such as the applications of third‐generation sequencing (TGS), single‐cell RNA sequencing (scRNA‐seq) and spatial transcriptomics (ST), will be desired with great expectations.ConclusionsTo our knowledge, the current review is the first one to evaluate the potential regulatory mechanisms of AS events in IBD. The expanding list of aberrantly spliced genes in IBD along with the developed technologies provide us new clues to how IBD develops, and how these important AS events can be explored for future treatment.

Multi-Omics Characterization of Colon Mucosa and Submucosa/Wall from Crohn’s Disease Patients

“…Among the different formats of proteoform, alternative splicing allows for the production of multiple splice isoforms from a single gene. mRNA splice isoforms have been shown to play a critical role in the onset of IBD, regulating various biological functions, including immune response, epithelial barrier, microbiota, and fibrosis [46]. However, identifying protein isoforms on a large-scale LC/MS-based shotgun proteomics is challenging, due to the sensitivity of instruments and the substantial number of degenerate peptides [47].…”

Intestinal strictures in Crohn's disease: An update from 2023

“…In the future, advancements in more sophisticated technologies such as SNP analysis and spatial multi‐omics will contribute to deeper understanding of the mechanisms underlying fibrosis. 87 With the help of AI, novel advancements in the field of intestinal fibrosis diagnosis are on the horizon. These advancements will contribute to the certification of new approaches for diagnosing and predicting intestinal fibrosis, as well as facilitate clinical research on anti‐fibrotic drugs.…”

“…omics will contribute to deeper understanding of the mechanisms underlying fibrosis 87. With the help of AI, novel advancements in the field of intestinal fibrosis diagnosis are on the horizon.…”

Expression of Truncated Products at the 5′-Terminal Region of RIPK2 and Evolutive Aspects that Support Their Biological Importance

“…Literature has presented many data on the involvement of abnormal AS in the occurrence of several biological processes, such as normal ageing ( Baralle and Romano 2023 ), premature ageing ( Lopez-Mejia, et al 2011 ) and age-related disorders, which range from hypertension to cardiovascular ( Hu, et al 2017 ; Gotthardt, et al 2023 ) and liver diseases ( Jobbins, et al 2023 ), neurodegeneration ( Nikom and Zheng 2023 ), and cancer ( Song, et al 2023 ; Temaj, et al 2023 ). Aberrant splicing is also implicated in processes that affect people of all ages, such as inflammatory bowel disease ( Zhou, et al 2023 ; Zou, et al 2023 ) and viral infection ( Mann, et al 2023 ). The mechanisms underlying the association of AS and diseases include alteration in splice site sequences and in cis- and trans-splicing regulatory elements ( Tang, et al 2020 ), chromatin modifications ( Gomez Acuna, et al 2013 ) and mutations that disrupt RNA secondary structure ( Warf and Berglund 2010 ), which can mediate mRNA decay or cause deletion of domains that are important for protein function.…”