Topic: R-loop Induced Genome Instability and Premature Aging

Speaker: Prof. Xiangdong FU

Time: 4:30-5:30 PM, 3 Aug. , 2023

Venue: Room 111, Lynn Library

Abstract：

Mutations in the Cockayne Syndrome group B (CSB) gene cause severe neurodevelopmental defects and premature aging. As a member of the SWI/SNF family of chromatin remodelers, CSB is best known for its role in transcription-coupled nucleotide excision (TC-NER), but this function neither explains the major disease phenotype nor offers any clue about the selective vulnerability in neurons. Pursuing Cockayne Syndrome-associated genome instability, we uncover an intrinsic mechanism by which elongating RNA polymerase II (RNAPII) undergoes transient pausing at internal T-runs where CSB is required to push RNAPII forward. Consequently, CSB deficiency retards RNAPII elongation in these regions, which is further amplified to induce genome instability via augmented R-loop formation. As such R-loop prone motifs are proportionally represented in long genes that predominately function in neurons, this mechanism provides critical insights into selective neuronal vulnerability.

Introduction：

Xiang-Dong Fu received his B.S. degree of Virology from Wuhan University in 1982. He was the first class of the CUSBEA for graduate training, obtaining his Ph.D. degree from Case Western Reserve University in 1988 and competed postdoctoral training at Harvard in 1988. In 1992, he joined the faculty at University of California, San Diego and became a Distinguished Professor in 2018. Since January 2023, he joined Westlake University as Chair Professor in RNA Biology and Regenerative Medicine.

Dr. Fu has made four sets of discoveries: (1) the first non-snRNP splicing factor SC35, which becomes a founding of the SR family of splicing regulators. (2) the SRPK family of splicing kinases that are highly specific for SR proteins. (3) the eRNAs expressed by active enhancers during transcriptional reprogramming, and a wide range of RNA binding proteins in diverse biological pathways (i.e., chromatin-associated function in regulating transcription and mediating co-transcriptional RNA processing). (4) a critical RNA program necessary and sufficient to trans-differentiate fibroblasts into functional neurons, which establishes a generalizable strategy for treatment of neurodegenerative diseases.

Dr. Fu’s contributions to biomedical research have been honored by selection or election as Searle Scholar (1994), Leukemia and Lymphoma Society Scholar (1997), AAAS Fellow (2010), the Ray Wu Society Award (2016), and Falling Walls Berlin for the Science Breakthroughs of Year 2020.