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Pre-mRNA splicing, which correctly recognizes exons fragmented by numerous introns and precisely joins exons together, is an essential process in gene expression, since mRNA is the blueprint for protein synthesis. On the other hand, the length of introns tends to increase in higher organisms, reaching its peak in humans, where the difference between long and short introns reaches over 40,000-fold. Textbooks typically describe splicing mechanisms that correspond to introns of a length favorable for research. Studies focusing on introns of extreme lengths have led to the discovery of new splicing molecular mechanisms. In very long introns, multi-step splicing within introns was found to be widely utilized. Conversely, in very short introns, we discovered a new splicing mechanism involving previously unknown factors.
It is a fact that in cancer, further extra splicing often occurs in spliced mature mRNAs, but such a catastrophic event should not happen in normal cells. We found that the suppressor factor of this abnormal mRNA re-splicing is the exon junction complex (EJC), which binds to the mature mRNA. This discovery is fundamental to the transcriptome quality control system and the key to elucidating the unknown mechanism of splicing completion.