HNRNPD regulates the biogenesis of circRNAs and the ratio of mRNAs to circRNAs for a set of genes
Shuhui Chang,
Yucong Wang,
Xiaolin Wang,
Hanyuan Liu,
Tao Zhang,
Yangge Zheng,
Xueren Wang,
Ge Shan,
Liang Chen
Affiliations
Shuhui Chang
Department of Laboratory Medicine, The First Affiliated Hospital of USTC, The RNA Institute, School of Basic Medical Sciences, Division of Life Science and Medicine, University of Science and Technology of China (USTC), Hefei, Anhui, China
Yucong Wang
Department of Laboratory Medicine, The First Affiliated Hospital of USTC, The RNA Institute, School of Basic Medical Sciences, Division of Life Science and Medicine, University of Science and Technology of China (USTC), Hefei, Anhui, China
Xiaolin Wang
Department of Laboratory Medicine, The First Affiliated Hospital of USTC, The RNA Institute, School of Basic Medical Sciences, Division of Life Science and Medicine, University of Science and Technology of China (USTC), Hefei, Anhui, China
Hanyuan Liu
Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China (USTC), Hefei, China
Tao Zhang
Department of Urology, the Second Affiliated Hospital of Anhui Medical University, Hefei, China
Yangge Zheng
Courant Institute of Mathematical Sciences, New York University, New York, USA
Xueren Wang
Department of Anesthesiology, Shanxi Bethune Hospital, Taiyuan, China
Ge Shan
Department of Laboratory Medicine, The First Affiliated Hospital of USTC, The RNA Institute, School of Basic Medical Sciences, Division of Life Science and Medicine, University of Science and Technology of China (USTC), Hefei, Anhui, China
Liang Chen
Department of Laboratory Medicine, The First Affiliated Hospital of USTC, The RNA Institute, School of Basic Medical Sciences, Division of Life Science and Medicine, University of Science and Technology of China (USTC), Hefei, Anhui, China
Exonic circular RNAs (ecircRNAs) in animal cells are generated by backsplicing, and the biogenesis of ecircRNAs is regulated by an array of RNA binding proteins (RBPs). HNRNPD is a heterogeneous nuclear ribonucleoprotein family member with both cytoplasmic and nuclear roles, and whether HNRNPD regulates the biogenesis of circRNAs remains unknown. In this study, we examine the role of HNRNPD in the biogenesis of ecircRNAs. The levels of ecircRNAs are primarily increased upon depletion of HNRNPD. HNRNPD preferentially binds to motifs enriched with A and U nucleotides, and the flanking introns of ecircRNAs tend to have more numbers and higher intensity of HNRNPD binding sites. The levels of mRNAs are generally not significantly altered in HNRNPD knockout cells. For a small set of genes, the circRNA:mRNA ratio is substantially affected, and the mRNA levels of some of these genes demonstrate a significant decrease in HNRNPD knockout cells. CDK1 is identified as a key gene modulated by HNRNPD in the context of circRNA biogenesis. HNRNPD suppresses the biogenesis of circCDK1 and favours the generation of CDK1 mRNA, and the CDK1 protein is a critical regulator of the cell cycle and apoptosis. HNRNPD can participate in cellular physiology, including the cell cycle and apoptosis, and plays roles in clear cell renal cell carcinoma (ccRCC) by modulating circRNA biogenesis and the mRNA levels of key genes, such as CDK1.
