Hai-Li Ma, Martin Bizet, Christelle Soares Da Costa, Frédéric Murisier, Eric James de Bony, Meng-Ke Wang, Akihide Yoshimi, Kuan-Ting Lin, Kristin M Riching, Xing Wang, John I Beckman, Shailee Arya, Nathalie Droin, Emilie Calonne, Bouchra Hassabi, Qing-Yang Zhang, Ang Li, Pascale Putmans, Lionel Malbec, Céline Hubert, Jie Lan, Frédérique Mies, Ying Yang, Eric Solary, Danette L Daniels, Yogesh K Gupta, Rachel Deplus, Omar Abdel-Wahab, Yun-Gui Yang, François Fuks
A common mRNA modification is 5-methylcytosine (m5 C), whose role in gene-transcript processing and cancer remains unclear. Here, we identify serine/arginine-rich splicing factor 2 (SRSF2) as a reader of m5 C and impaired SRSF2 m5 C binding as a potential contributor to leukemogenesis. Structurally, we identify residues involved in m5 C recognition and the impact of the prevalent leukemia-associated mutation SRSF2P95H . We show that SRSF2 binding and m5 C colocalize within transcripts. Furthermore, knocking down the m5 C writer NSUN2 decreases mRNA m5 C, reduces SRSF2 binding, and alters RNA splicing...
December 7, 2023: Molecular Cell