HNRNPD regulates the biogenesis of circRNAs and the ratio of mRNAs to circRNAs for a set of genes

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 regul...

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Main Authors: Shuhui Chang, Yucong Wang, Xiaolin Wang, Hanyuan Liu, Tao Zhang, Yangge Zheng, Xueren Wang, Ge Shan, Liang Chen
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:RNA Biology
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Online Access:https://www.tandfonline.com/doi/10.1080/15476286.2024.2386500
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author Shuhui Chang
Yucong Wang
Xiaolin Wang
Hanyuan Liu
Tao Zhang
Yangge Zheng
Xueren Wang
Ge Shan
Liang Chen
author_facet Shuhui Chang
Yucong Wang
Xiaolin Wang
Hanyuan Liu
Tao Zhang
Yangge Zheng
Xueren Wang
Ge Shan
Liang Chen
author_sort Shuhui Chang
collection DOAJ
description 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.
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spelling doaj-art-1a9dfde8bb574660bad67664f21eaaaf2025-08-20T01:59:08ZengTaylor & Francis GroupRNA Biology1547-62861555-85842024-12-0121183484810.1080/15476286.2024.2386500HNRNPD regulates the biogenesis of circRNAs and the ratio of mRNAs to circRNAs for a set of genesShuhui Chang0Yucong Wang1Xiaolin Wang2Hanyuan Liu3Tao Zhang4Yangge Zheng5Xueren Wang6Ge Shan7Liang Chen8Department 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment of Urology, the Second Affiliated Hospital of Anhui Medical University, Hefei, ChinaCourant Institute of Mathematical Sciences, New York University, New York, USADepartment of Anesthesiology, Shanxi Bethune Hospital, Taiyuan, ChinaDepartment 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, ChinaDepartment 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, ChinaExonic 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.https://www.tandfonline.com/doi/10.1080/15476286.2024.2386500HNRNPDcircRNAbiogenesisCDK1ccRCC
spellingShingle Shuhui Chang
Yucong Wang
Xiaolin Wang
Hanyuan Liu
Tao Zhang
Yangge Zheng
Xueren Wang
Ge Shan
Liang Chen
HNRNPD regulates the biogenesis of circRNAs and the ratio of mRNAs to circRNAs for a set of genes
RNA Biology
HNRNPD
circRNA
biogenesis
CDK1
ccRCC
title HNRNPD regulates the biogenesis of circRNAs and the ratio of mRNAs to circRNAs for a set of genes
title_full HNRNPD regulates the biogenesis of circRNAs and the ratio of mRNAs to circRNAs for a set of genes
title_fullStr HNRNPD regulates the biogenesis of circRNAs and the ratio of mRNAs to circRNAs for a set of genes
title_full_unstemmed HNRNPD regulates the biogenesis of circRNAs and the ratio of mRNAs to circRNAs for a set of genes
title_short HNRNPD regulates the biogenesis of circRNAs and the ratio of mRNAs to circRNAs for a set of genes
title_sort hnrnpd regulates the biogenesis of circrnas and the ratio of mrnas to circrnas for a set of genes
topic HNRNPD
circRNA
biogenesis
CDK1
ccRCC
url https://www.tandfonline.com/doi/10.1080/15476286.2024.2386500
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