动物细胞中的外显子环状 RNA (ecircRNA) 是通过反向剪接产生的，ecircRNA 的生物发生受到一系列 RNA 结合蛋白 (RBP) 的调节。 HNRNPD 是一种异质核核糖核蛋白家族成员，具有细胞质和核作用，HNRNPD 是否调节 circRNA 的生物合成仍不清楚。在这项研究中，我们研究了 HNRNPD 在 ecircRNA 生物发生中的作用。 ecircRNA 的水平主要在 HNRNPD 耗尽后增加。 HNRNPD 优先结合富含 A 和 U 核苷酸的基序，并且 ecircRNA 的侧翼内含子往往具有更多数量和更高强度的 HNRNPD 结合位点。 HNRNPD 敲除细胞中 mRNA 的水平通常不会显着改变。对于一小部分基因，circRNA:mRNA 比率受到显着影响，其中一些基因的 mRNA 水平在 HNRNPD 敲除细胞中表现出显着降低。 CDK1 被认为是 circRNA 生物发生过程中受 HNRNPD 调节的关键基因。 HNRNPD 抑制 circCDK1 的生物发生并有利于 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 可以参与细胞生理学，包括细胞周期和细胞凋亡，并通过调节 circRNA 生物发生和关键基因（如 CDK1）的 mRNA 水平在透明细胞肾细胞癌（ccRCC）中发挥作用。

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.