Hnrnpd, also known as AUF1, is a heterogeneous nuclear ribonucleoprotein family member with both cytoplasmic and nuclear roles. It binds to RNA and is involved in post-transcriptional regulation, participating in processes like nuclear export, stability, and translation of specific transcripts [2]. It's associated with multiple cellular pathways, and its dysregulation is linked to various diseases, making it an important gene for understanding cellular physiology and disease mechanisms.

Depletion of Hnrnpd primarily increases the levels of exonic circular RNAs (ecircRNAs), and it preferentially binds to A-and U-rich motifs, with ecircRNA-flanking introns having more Hnrnpd binding sites. For some genes like CDK1, Hnrnpd suppresses circCDK1 biogenesis and favors CDK1 mRNA generation, affecting the cell cycle and apoptosis in clear cell renal cell carcinoma (ccRCC) [1]. In other studies, knockdown of Hnrnpd in non-small cell lung cancer (NSCLC) cell lines reduces cell proliferation, invasion, and metastatic capacity via the PI3K-AKT pathway, indicating its role in cancer progression [4]. In hepatocellular carcinoma, circLARP1B binds to Hnrnpd in the cytoplasm, affecting the binding of Hnrnpd to LKB1 mRNA, leading to decreased LKB1 mRNA stability and promoting metastasis and lipid accumulation [3].

In summary, Hnrnpd plays essential roles in post-transcriptional regulation, influencing processes such as circRNA biogenesis, mRNA stability, and translation. Its dysregulation is implicated in multiple diseases, especially various cancers. Studies using gene-knockout or knockdown models in cell lines and in vivo (such as in mouse models) have been crucial in uncovering these functions, providing insights into disease mechanisms and potential therapeutic targets.

References:

1. Chang, Shuhui, Wang, Yucong, Wang, Xiaolin, Shan, Ge, Chen, Liang. 2024. HNRNPD regulates the biogenesis of circRNAs and the ratio of mRNAs to circRNAs for a set of genes. In RNA biology, 21, 1-15. doi:10.1080/15476286.2024.2386500. https://pubmed.ncbi.nlm.nih.gov/39180763/

2. Kattan, Fedon-Giasin, Koukouraki, Pelagia, Anagnostopoulos, Athanasios K, Tsangaris, George T, Doxakis, Epaminondas. 2023. RNA binding protein AUF1/HNRNPD regulates nuclear export, stability and translation of SNCA transcripts. In Open biology, 13, 230158. doi:10.1098/rsob.230158. https://pubmed.ncbi.nlm.nih.gov/37989221/

3. Li, Jingxin, Wang, Xiaolin, Shi, Liang, Cai, Xiujun, Shan, Ge. 2023. A Mammalian Conserved Circular RNA CircLARP1B Regulates Hepatocellular Carcinoma Metastasis and Lipid Metabolism. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 11, e2305902. doi:10.1002/advs.202305902. https://pubmed.ncbi.nlm.nih.gov/37953462/

4. Fan, Guoqing, Li, Danni, Liu, Jingjing, Cai, Jianping, Sun, Tieying. 2023. HNRNPD is a prognostic biomarker in non-small cell lung cancer and affects tumor growth and metastasis via the PI3K-AKT pathway. In Biotechnology & genetic engineering reviews, 40, 1571-1590. doi:10.1080/02648725.2023.2196155. https://pubmed.ncbi.nlm.nih.gov/36971333/