HuR binds to flanking exons and regulates intron retention alternative splicing of cell cycle-related genes in smooth muscle cells

The RNA-binding protein HuR influences gene stability and translation, promoting vascular smooth muscle cell proliferation and being linked to inflammation. However, there is a paucity of studies focusing on the role of in HuR in vascular smooth muscle cells. Knocking down HuR in cerebral vascular smooth muscle cells altered gene expression, with 3,300 genes upregulated in cytokine signaling pathways and 1,998 downregulated in cell mitosis pathways. It also affected alternative splicing, resulting in 3,531 events mainly related to RNA splicing and the cell cycle. Pearson analysis linked 33 splicing events with gene expression, including cell cycle genes MCM5, UHRF1, RPA2, and PRC1. eCLIP-seq of HuR identified 5,582 binding peaks in CDS and 3'UTR regions, with 33 related to cell cycle genes like Atf5, Ier3, and Zfp36l2. This study is the first to explore how the HuR gene influences cell cycle gene expression through pre-mRNA alternative splicing in vascular smooth muscle cells, enhancing our understanding of HuR's role in cardiovascular diseases.