LongTREC presents:
Long-read transcriptome sequencing of CLL and MDS patients uncovers molecular effects of SF3B1 mutations
Alicja Pacholewska, Matthias Lienhard, Mirko Brüggemann, Heike Hänel, Lorina Bilalli, Anja Königs, Felix Heß, Kerstin Becker, Karl Köhrer, Jesko Kaiser, Holger Gohlke, Norbert Gattermann, Michael Hallek, Carmen D. Herling, Julian König, Christina Grimm, Ralf Herwig, Kathi Zarnack, Michal R. Schweiger
Before a gene’s RNA message can be used, it is edited: some pieces are cut out and the rest are joined together, a process called splicing. SF3B1 is a key protein in this editing machinery, and mutations in it are common in two blood cancers: chronic lymphocytic leukemia (CLL) and myelodysplastic syndromes (MDS). Curiously, these mutations are linked to a better prognosis in MDS but a worse one in CLL.
To understand what these mutations do, the researchers applied long-read transcriptome sequencing, which reads complete RNA molecules, to 44 patients and to cell lines with and without the mutation. More than 60% of the RNA versions (isoforms) they found were new. Splicing changes were largely shared between both cancers and especially affected the points where RNA pieces are joined. Combining these data with RNA-binding maps and computer simulations, they also predicted how the mutated protein binds RNA less well.
This is the most complete long-read study so far of SF3B1 mutations in these cancers. Besides clarifying how the mutation disrupts splicing, it provides a valuable resource for researchers studying faulty RNA splicing in cancer.
Read the full text here: https://doi.org/10.1101/gr.279327.124
