Nature Communications (Feb 2023)
Splicing factor SRSF1 deficiency in the liver triggers NASH-like pathology and cell death
- Waqar Arif,
- Bhoomika Mathur,
- Michael F. Saikali,
- Ullas V. Chembazhi,
- Katelyn Toohill,
- You Jin Song,
- Qinyu Hao,
- Saman Karimi,
- Steven M. Blue,
- Brian A. Yee,
- Eric L. Van Nostrand,
- Sushant Bangru,
- Grace Guzman,
- Gene W. Yeo,
- Kannanganattu V. Prasanth,
- Sayeepriyadarshini Anakk,
- Carolyn L. Cummins,
- Auinash Kalsotra
Affiliations
- Waqar Arif
- Department of Biochemistry, University of Illinois Urbana-Champaign
- Bhoomika Mathur
- Department of Molecular and Integrative Physiology, University of Illinois Urbana-Champaign
- Michael F. Saikali
- Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto
- Ullas V. Chembazhi
- Department of Biochemistry, University of Illinois Urbana-Champaign
- Katelyn Toohill
- Department of Biochemistry, University of Illinois Urbana-Champaign
- You Jin Song
- Department of Cell and Developmental Biology, University of Illinois Urbana-Champaign
- Qinyu Hao
- Department of Cell and Developmental Biology, University of Illinois Urbana-Champaign
- Saman Karimi
- Department of Pathology, College of Medicine, Cancer Center, University of Illinois Hospital and Health Science Chicago
- Steven M. Blue
- Department of Cellular and Molecular Medicine, University of California at San Diego
- Brian A. Yee
- Department of Cellular and Molecular Medicine, University of California at San Diego
- Eric L. Van Nostrand
- Department of Cellular and Molecular Medicine, University of California at San Diego
- Sushant Bangru
- Department of Biochemistry, University of Illinois Urbana-Champaign
- Grace Guzman
- Department of Pathology, College of Medicine, Cancer Center, University of Illinois Hospital and Health Science Chicago
- Gene W. Yeo
- Department of Cellular and Molecular Medicine, University of California at San Diego
- Kannanganattu V. Prasanth
- Department of Cell and Developmental Biology, University of Illinois Urbana-Champaign
- Sayeepriyadarshini Anakk
- Department of Molecular and Integrative Physiology, University of Illinois Urbana-Champaign
- Carolyn L. Cummins
- Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto
- Auinash Kalsotra
- Department of Biochemistry, University of Illinois Urbana-Champaign
- DOI
- https://doi.org/10.1038/s41467-023-35932-3
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 19
Abstract
Nonalcoholic steatohepatitis (NASH) is an advanced form of fatty liver disease with complex pathogenic mechanisms. Here, the authors report that SRSF1 deficiency in mice livers provokes deleterious R-loop formation and genotoxicity, which impedes hepatocellular gene expression, metabolism, and lipid trafficking, resulting in NASH-like pathology.
