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

IF 3.6 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY RNA Biology Pub Date : 2024-01-01 Epub Date: 2024-08-24 DOI:10.1080/15476286.2024.2386500
Shuhui Chang, Yucong Wang, Xiaolin Wang, Hanyuan Liu, Tao Zhang, Yangge Zheng, Xueren Wang, Ge Shan, Liang Chen
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Abstract

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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HNRNPD 可调节 circRNA 的生物生成以及一组基因的 mRNA 与 circRNA 的比例。
动物细胞中的外显子环状RNA(ecircRNAs)是通过反拼接产生的,而ecircRNAs的生物发生受一系列RNA结合蛋白(RBPs)的调控。 HNRNPD是一种异质性核核糖核蛋白家族成员,具有细胞质和细胞核的双重作用,而HNRNPD是否调控circRNAs的生物发生仍是未知数。本研究探讨了 HNRNPD 在 ecircRNAs 生物发生过程中的作用。消耗 HNRNPD 后,ecircRNAs 的水平主要会增加。HNRNPD 优先与富含 A 和 U 核苷酸的基团结合,ecircRNA 的内含子侧翼往往有更多和更高强度的 HNRNPD 结合位点。在 HNRNPD 基因敲除的细胞中,mRNA 的水平一般不会发生显著变化。对于一小部分基因,circRNA:mRNA 的比例会受到很大影响,其中一些基因的 mRNA 水平在 HNRNPD 基因敲除细胞中会显著下降。CDK1 被确定为在 circRNA 生物发生过程中受 HNRNPD 调节的关键基因。HNRNPD 抑制了 circCDK1 的生物发生,有利于 CDK1 mRNA 的生成,而 CDK1 蛋白是细胞周期和细胞凋亡的关键调节因子。HNRNPD 可参与细胞生理,包括细胞周期和细胞凋亡,并通过调节 circRNA 的生物生成和 CDK1 等关键基因的 mRNA 水平,在透明细胞肾细胞癌(ccRCC)中发挥作用。
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来源期刊
RNA Biology
RNA Biology 生物-生化与分子生物学
CiteScore
8.60
自引率
0.00%
发文量
82
审稿时长
1 months
期刊介绍: RNA has played a central role in all cellular processes since the beginning of life: decoding the genome, regulating gene expression, mediating molecular interactions, catalyzing chemical reactions. RNA Biology, as a leading journal in the field, provides a platform for presenting and discussing cutting-edge RNA research. RNA Biology brings together a multidisciplinary community of scientists working in the areas of: Transcription and splicing Post-transcriptional regulation of gene expression Non-coding RNAs RNA localization Translation and catalysis by RNA Structural biology Bioinformatics RNA in disease and therapy
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