Author response: Cross-talk between PRMT1-mediated methylation and ubiquitylation on RBM15 controls RNA splicing
Year: 2015
Type: peer-review
Abstract: The many different cell types in an adult animal all develop from a single fertilized egg. The development of cells into more specialized cell types is called ‘differentiation’. Proteins and other molecules from both inside and outside of the cells regulate the differentiation process. RNA is a molecule that is similar to DNA, and performs several important roles inside cells. Perhaps most importantly, RNA molecules act as messengers and carry genetic instructions during gene expression. RBM15 is an RNA-binding protein that is found throughout nature, and is involved in a number of developmental processes. Previous research has linked the incorrect control of RBM15 with an increased risk of certain cancers, including megakaryocytic leukemia. However, it is not clear what role RNA-binding proteins such as RBM15 play during differentiation. Now, Zhang, Tran, Su et al. have investigated the role of RBM15 during the development of large cells found in human bone marrow (called megakaryocytes). First, the experiments demonstrated that an enzyme called PRMT1 modifies RBM15. This enzyme adds a chemical mark called a methyl group at a specific site (an arginine amino acid) on the RNA-binding protein. Next, Zhang, Tran, Su et al. showed that the addition of this methyl group earmarks RBM15 for destruction. This means that an increase in PRMT1 levels reduces the amount of RBM15 in cells, while decreases in PRMT1 have the opposite effect. Further experiments showed that RBM15 normally processes the RNA messengers that carry the genetic instructions needed for the differentiation of bone marrow cells. An excess of PRMT1 enzyme leads to a lack of this RNA-binding protein. This in turn interferes with the differentiation process, and can contribute to the development of cancers such as megakaryocytic leukemia. Future work will therefore explore whether targeting PRMT1 with drugs could represent an effective treatment for these kinds of cancers.
Authors: Li Zhang, Ngoc-Tung Tran, Hairui Su, Rui Wang, Yuheng Lu, Haiping Tang, Sayura Aoyagi, Ailan Guo, Alireza Khodadadi-Jamayran, Dewang Zhou, Kun Qian, Todd Hricik, Jocelyn Côté, Xiaosi Han, Wenping Zhou, Suparna Laha, Omar Abdel-Wahab, Ross L Levine, Glen Raffel, Yanyan Liu, Dongquan Chen, Haitao Li, Tim Townes, Hengbin Wang, Haiteng Deng, Y George Zheng, Christina Leslie, Minkui Luo, Xinyang Zhao
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W2983815465