​[SBS Seminar]​​​ SRRM2 organizes splicing condensates to regulate alternative splicing in human myeloid cells

15 Jan 2021 04.00 PM - 06.00 PM Classroom 1, SBS Current Students

Our lab studies splicing mechanisms and their implications in human genetic diseases including cancer As a major research line, we recently profiled alternative splicing in human myeloid cells such as monocytes/macrophages and neutrophils In this seminar, I will present one subproject centered on the SRRM 2 splicing factor, which we identified as a key player in human myeloid cells, likely both in physiology and leukemia SRRM 2 was known as a nuclear speckle marker containing multiple disordered domains, and we now show that it forms biomolecular condensates in human cells with hallmarks of liquid liquid phase separation By live cell imaging, we found that SRRM 2 is responsible for organizing nuclear speckles through cell cycle Our transcriptomic data in THP 1 monocyte like cells show that SRRM 2 deficiency mainly induces skipping of cassette exons with specific properties, and that it acts co transcriptionally Functionally, SRRM 2 regulates several splicing events important for myeloid cells, including production
of a FES splice isoform that attenuates innate inflammatory responses Our long term goal is to connect SRRM 2
condensate formation with splicing regulation and cellular function Our results reveal that SRRM 2 acts as a scaffold to
organize nuclear speckles likely via phase separation, which in turn regulates alternative splicing in innate immunity