Clark Madeline E, Farinha Andrew, Morrison Alan R, Lisi George P
Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI 02903, United States.
Departments of Research and Medicine, Vascular Research Laboratory, Providence VA Medical Center, Providence, RI 02908, United States.
NAR Mol Med. 2025 Feb 3;2(1):ugaf002. doi: 10.1093/narmme/ugaf002. eCollection 2025 Jan.
Human antigen R (HuR) is a ubiquitously expressed RNA-binding protein (RBP) that has been implicated in a vast range of biological processes including stress response, angiogenesis, cell proliferation, and differentiation. Dysregulation of HuR has been linked to a number of pathological disorders including vascular disease, inflammation, and cancers such as those of the breast and colon. Like many RBPs, HuR is composed of multiple RNA-recognition motif (RRM) domains; however, HuR and the three other members of the Hu family (HuB, HuC, and HuD) possess a unique structural composition with two RRMs separated from a third C-terminal RRM by a long, unstructured hinge region. While there has been extensive research on the role of HuR in cellular, molecular, and developmental biology, there are fewer structural and biochemical studies of HuR and many questions still remain about the molecular mechanisms of HuR. In this review, we endeavor to synthesize existing HuR research spanning the last three decades in order to define known mechanistic roles of each domain, highlight remaining uncertainties, and provide a backdrop for ongoing research into the chemistry and biology of HuR and similar multi-RRM containing proteins.
人抗原R（HuR）是一种广泛表达的RNA结合蛋白（RBP），它参与了包括应激反应、血管生成、细胞增殖和分化在内的大量生物学过程。HuR的失调与许多病理疾病有关，包括血管疾病、炎症以及乳腺癌和结肠癌等癌症。与许多RBP一样，HuR由多个RNA识别基序（RRM）结构域组成；然而，HuR以及Hu家族的其他三个成员（HuB、HuC和HuD）具有独特的结构组成，两个RRM通过一个长的无结构铰链区与第三个C末端RRM分开。虽然对HuR在细胞、分子和发育生物学中的作用进行了广泛研究，但对HuR的结构和生化研究较少，关于HuR的分子机制仍有许多问题。在这篇综述中，我们努力综合过去三十年中现有的HuR研究，以确定每个结构域已知的机制作用，突出仍然存在的不确定性，并为正在进行的关于HuR和类似含多个RRM的蛋白质的化学和生物学研究提供背景。
