What Makes Blood Stem Cells Transform? Regulation of RNA Splicing May Be an Answer
Published:23 Apr.2023 Source:Lund University
Researchers at Lund University Faculty of Medicine have determined a novel mechanism linking the metabolism of ribonucleic acids, RNA, to the development of leukemia in myelodysplastic syndrome patients, MDS. In a study published in the Molecular Cell journal, they explain what makes hematopoietic stem cells acquire malignant traits in cancer.
RNA splicing is a major nexus of gene expression regulation, shaping cellular identity during development, frequently altered in human cancers. This process is mediated by a complex molecular machinery known as the spliceosome, which enables the production of multiple and functionally distinct proteins from single genes.
A team of researchers led by Dr. Cristian Bellodi recently discovered a hardwired genetic control mechanism modulating individual spliceosomal components, known as splicing factors, in cells harboring oncogenic lesions common in human cancers.This work highlighted core splicing proteins, including SF3B1, frequently mutated in various cancers. Splicing factor mutations are particularly prevalent in MDS, a group of heterogeneous hematological disorders characterized by defective blood stem cells and a high risk of leukemia development.
The authors further investigated the molecular determinants controlling the SF3B1 production during the transition to leukemia. These studies led to the breakthrough discovery that SF3B1 synthesis depends on a single RNA chemical modification mark, known as N6-methyladenosine, m6A, deposited on its messenger RNA.