Aberrant splicing and defective mRNA production induced by somatic spliceosome mutations in myelodysplasia.

ABSTRACT: Spliceosome mutations are frequently found in myelodysplasia. Splicing alterations induced by these mutations, their precise targets, and the effect at the transcript level have not been fully elucidated. Here we report transcriptomic analyses of 265 bone marrow samples from myelodysplasia patients, followed by a validation using CRISPR/Cas9-mediated gene editing and an assessment of nonsense-mediated decay susceptibility. Small but widespread reduction of intron-retaining isoforms is the most frequent splicing alteration in SF3B1-mutated samples. SF3B1 mutation is also associated with 3' splice site alterations, leading to the most pronounced reduction of canonical transcripts. Target genes include tumor suppressors and genes of mitochondrial iron metabolism or heme biosynthesis. Alternat

SUBMITTER: Shiozawa Y 

PROVIDER: S-EPMC6128865 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature