Polr2a, also known as RNA polymerase II subunit A, encodes the largest subunit of DNA-dependent RNA polymerase II. This enzyme is crucial for transcription, the process of synthesizing RNA from DNA, and thus is involved in regulating gene expression, a fundamental biological process. It is associated with various cellular pathways related to growth, development, and homeostasis [1-10]. Genetic models, such as gene-knockout (KO) or conditional-knockout (CKO) mouse models, are valuable tools for studying Polr2a's functions.

In a KO mouse model, osteoclast-specific deletion of Polr2a blocked bone resorption in vivo, indicating its role in osteoclastogenesis and potential relevance in osteoporosis [1]. In gastric cancer, Polr2a promoted cell proliferation both in vitro and in vivo, advanced the overall cell cycle progression, inhibited cell apoptosis, and promoted cell migration, suggesting its oncogenic role [2]. In triple-negative breast cancer, in silico analysis identified Polr2a as a collateral vulnerability target, and its inhibition via small interfering RNA (siRNA) showed potential for targeted treatment [3]. In addition, de novo germline mutations in Polr2a were associated with a neurodevelopmental disorder, with phenotypes including ataxia, joint hypermobility, and epilepsy [4]. A case of ependymoma was reported in a patient with a de novo pathogenic variant in Polr2a, suggesting a possible link between Polr2a variants and cancer predisposition [5].

In conclusion, Polr2a is essential for transcription and gene expression regulation. Model-based research, especially KO/CKO mouse models, has revealed its roles in multiple biological processes and disease conditions, including osteoporosis, various cancers, and neurodevelopmental disorders. Understanding Polr2a's functions provides insights into disease mechanisms and may offer potential therapeutic targets.