Exitron

Even though they are considered introns, which are typically cut out of pre mRNA sequences, there are significant problems that arise when exitrons are spliced out of these strands, with the most obvious result being altered protein structures and functions.

[2] Splicing mutations of a mRNA sequence has been found to account for 15-60% of human genetic diseases, which suggests there may be a crucial role of exitrons in organ homeostasis.

[3][4] A previous study had looked at alternative splicing in Rockcress (Arabidopsis) plants and pinpointed characteristics of retained introns in sequences.

[7] This study revealed exitron splicing disrupts functional protein domains, causing cancer driver effects and introducing a new potential source of neoantigens.

[6] (4) exitrons had distinct cis-acting features such as weak 5′ and 3′ splice sites, high GC content, and short length compared to retained introns.

[6] Exitron sequences contain sites for numerous post-translational modifications, including sumoylation, ubiquitylation, S-nitrosylation, and lysine acetylation.

One of the significantly exitron-spliced genes (SEGs), NEFH, which rarely experiences mutations, was identified as a novel tumor suppressor in prostate cancer.

Exitron splicing has the potential to introduce highly immunogenic neoantigens, which can be targetable with immunotherapy, thereby providing a promising avenue for cancer treatment.