Wei Lu, Lai Eric C
Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Developmental Biology Program, Sloan Kettering Institute, New York, NY, United States.
Front Genet. 2022 Feb 23;13:848626. doi: 10.3389/fgene.2022.848626. eCollection 2022.
The process of alternative polyadenylation (APA) generates multiple 3' UTR isoforms for a given locus, which can alter regulatory capacity and on occasion change coding potential. APA was initially characterized for a few genes, but in the past decade, has been found to be the rule for metazoan genes. While numerous differences in APA profiles have been catalogued across genetic conditions, perturbations, and diseases, our knowledge of APA mechanisms and biology is far from complete. In this review, we highlight recent findings regarding the role of the conserved ELAV/Hu family of RNA binding proteins (RBPs) in generating the broad landscape of lengthened 3' UTRs that is characteristic of neurons. We relate this to their established roles in alternative splicing, and summarize ongoing directions that will further elucidate the molecular strategies for neural APA, the functions of ELAV/Hu RBPs, and the phenotypic consequences of these regulatory paradigms in neurons.
可变聚腺苷酸化（APA）过程会为给定基因座产生多个3'UTR异构体，这可能会改变调控能力，有时还会改变编码潜力。APA最初是在少数基因中得到表征的，但在过去十年中，已发现它是后生动物基因的普遍规律。虽然在各种遗传条件、扰动和疾病中，APA图谱的众多差异已被编目，但我们对APA机制和生物学的了解还远远不够完整。在这篇综述中，我们重点介绍了关于保守的ELAV/Hu家族RNA结合蛋白（RBPs）在产生神经元特有的广泛延长3'UTR景观中所起作用的最新发现。我们将此与它们在可变剪接中已确立的作用联系起来，并总结了正在进行的研究方向，这些方向将进一步阐明神经APA的分子策略、ELAV/Hu RBPs的功能以及这些调控模式在神经元中的表型后果。
