Paira Sunirmal, Borden Katherine L B
Department of Pharmacology, Northwestern University, Chicago, IL, USA.
Robert H Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Department of Pharmacology, Northwestern University, Chicago, IL, USA.
RNA Biol. 2025 Dec;22(1):1-14. doi: 10.1080/15476286.2025.2503040. Epub 2025 Jun 9.
mRNAs undergo a series of chemical modifications to become competent for nuclear export and translation. This is referred to as mRNA maturation or processing and includes capping, splicing, and 3'end formation. These steps can be hijacked in cancer to alter proteins' forms and levels in the absence of mutation or changes to transcript levels. Here, we focus on an emerging idea that some factors act in multiple processing events and that their dysregulation in both their canonical and noncanonical functions contributes to cancer with a focus on Acute Myeloid Leukaemia (AML). As examples, we discuss the eukaryotic translation initiation factor (eIF4E), splice factor 3 complex B subunit 1 (SF3B1), U2 small nuclear auxiliary factor (U2AF1), and associated factors. These physically interact with each other and play roles in splicing, export, and translation. Malignant dysregulation of this mRNA processing-export-translation axis diversifies the proteome to support cancer. Finally, we discuss the simultaneous dysregulation of mRNA processing in malignancy and related therapeutic development.
信使核糖核酸（mRNAs）会经历一系列化学修饰，从而具备进行核输出和翻译的能力。这一过程被称为mRNA成熟或加工，包括加帽、剪接和3'端形成。在癌症中，这些步骤可能会被劫持，从而在不存在突变或转录水平变化的情况下改变蛋白质的形式和水平。在这里，我们关注一个新出现的观点，即一些因子在多个加工事件中发挥作用，并且它们在其经典和非经典功能中的失调都与癌症的发生有关，本文重点讨论急性髓系白血病（AML）。作为例子，我们讨论真核生物翻译起始因子（eIF4E）、剪接因子3复合物B亚基1（SF3B1）、U2小核辅助因子（U2AF1）以及相关因子。这些因子彼此之间存在物理相互作用，并在剪接、输出和翻译过程中发挥作用。这种mRNA加工-输出-翻译轴的恶性失调使蛋白质组多样化，从而支持癌症的发展。最后，我们讨论了恶性肿瘤中mRNA加工的同时失调以及相关治疗方法的开发。
