Decoding of exon splicing patterns in the human RUNX1-RUNX1T1 fusion gene

The International Journal of Biochemistry & Cell Biology
Vasily V GrinevOlga V Aleinikova

Abstract

The t(8;21) translocation is the most widespread genetic defect found in human acute myeloid leukemia. This translocation results in the RUNX1-RUNX1T1 fusion gene that produces a wide variety of alternative transcripts and influences the course of the disease. The rules of combinatorics and splicing of exons in the RUNX1-RUNX1T1 transcripts are not known. To address this issue, we developed an exon graph model of the fusion gene organization and evaluated its local exon combinatorics by the exon combinatorial index (ECI). Here we show that the local exon combinatorics of the RUNX1-RUNX1T1 gene follows a power-law behavior and (i) the vast majority of exons has a low ECI, (ii) only a small part is represented by "exons-hubs" of splicing with very high ECI values, and (iii) it is scale-free and very sensitive to targeted skipping of "exons-hubs". Stochasticity of the splicing machinery and preferred usage of exons in alternative splicing can explain such behavior of the system. Stochasticity may explain up to 12% of the ECI variance and results in a number of non-coding and unproductive transcripts that can be considered as a noise. Half-life of these transcripts is increased due to the deregulation of some key genes of the nonse...Continue Reading

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Citations

Aug 14, 2019·Wiley Interdisciplinary Reviews. RNA·Carla NecklesNatasha J Caplen
Jul 15, 2017·Molecular Genetics and Genomics : MGG·Tatsiana V Ramanouskaya, Vasily V Grinev
Jan 24, 2021·Nature Communications·Vasily V GrinevOlaf Heidenreich

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