Polr2d-KO Mouse

Polr2d, also known as RPB4, encodes a subunit of DNA-directed RNA polymerase II (pol II). The pol II enzyme, composed of ten core and two dissociable subunits, is crucial for transcribing DNA into RNA. The dissociable subcomplex of pol II, where Polr2d is a part, is a heterodimer with Rpb7/Polr2g. Polr2d is involved in pol II-mediated RNA synthesis and various mRNA regulations like pre-mRNA splicing, nuclear export of mRNAs, and mRNA decay [1].

In zebrafish, polr2d-deficient mutants exhibited progressive delay of somitogenesis starting at 11 h post-fertilization, increased cell death at 15 hpf, hypoplasia such as small eye and cardiac edema by 48 hpf, and premature death by 60 hpf. RT-qPCR showed diminished expression of housekeeping and zygotic genes in these mutants, indicating that Polr2d is indispensable for vertebrate development [1]. In mouse oocyte maturation, knockdown of Mat2b led to aberrant expression of Polr2d along with other maternal transcripts, and Mat2b was shown to play an important role in mouse oocyte maturation through the MAPK signaling pathway [2]. In pan-cancer analysis, POLR2D was identified as a commonly overexpressed and prognostic gene, and its knockdown decreased cell proliferation, suggesting a role in cancer-related cell growth [3]. In colon adenocarcinoma, POLR2D was part of a 16-metabolic-gene model that could predict patient survival prognosis [4].

In summary, Polr2d is essential for vertebrate development, playing key roles in processes like somitogenesis and maintaining proper gene expression. In addition, it is involved in mouse oocyte maturation through related signaling pathways. Its abnormal expression is associated with cancer cell growth and can be used as a biomarker for predicting colon adenocarcinoma prognosis. The study of Polr2d knockout models in zebrafish and other findings related to its expression changes in mouse oocytes and cancer cells have deepened our understanding of its functions in development and disease.

References:

1. Maeta, Masanari, Kataoka, Miku, Nishiya, Yusuke, Kashima, Makoto, Hirata, Hiromi. 2020. RNA polymerase II subunit D is essential for zebrafish development. In Scientific reports, 10, 13213. doi:10.1038/s41598-020-70110-1. https://pubmed.ncbi.nlm.nih.gov/32764610/

2. An, Quanli, Sun, Hongzheng, Zhang, Jun, Zhang, Yong, Su, Jianmin. 2020. Methionine Adenosyltransferase 2β Participates in Mouse Oocyte Maturation by Regulating the MAPK Pathway. In Reproductive sciences (Thousand Oaks, Calif.), 27, 163-171. doi:10.1007/s43032-019-00015-6. https://pubmed.ncbi.nlm.nih.gov/32046373/

3. Bhandari, Nikita, Acharya, Disha, Chatterjee, Annesha, Malakar, Pushkar, Shukla, Sudhanshu K. 2023. Pan-cancer integrated bioinformatic analysis of RNA polymerase subunits reveal RNA Pol I member CD3EAP regulates cell growth by modulating autophagy. In Cell cycle (Georgetown, Tex.), 22, 1986-2002. doi:10.1080/15384101.2023.2265676. https://pubmed.ncbi.nlm.nih.gov/37795959/

4. Zhao, Fuqiang, Liu, Yanlong, Gu, Xinyue, Song, Chengxin, Cui, Binbin. . Identification of sixteen metabolic genes as potential biomarkers for colon adenocarcinoma. In Journal of B.U.ON. : official journal of the Balkan Union of Oncology, 26, 1252-1259. doi:. https://pubmed.ncbi.nlm.nih.gov/34564978/