Université de Strasbourg, Architecture et Réactivité de l'ARN, Institut de Biologie Moléculaire et Cellulaire du CNRS, Strasbourg, France.
Department of Microbiology Medicine, New York University, New York, USA.
Bioessays. 2024 Nov;46(11):e2400173. doi: 10.1002/bies.202400173. Epub 2024 Sep 9.
While Dicer plays an important antiviral role through the RNAi pathway in plants and invertebrates, its contribution to antiviral immunity in vertebrates and more specifically mammals is more controversial. The apparent limited RNAi activity in mammalian cells has been attributed to the reduced long dsRNA processive activity of mammalian Dicer, as well as a functional incompatibility between the RNAi and IFN pathways. Why Dicer has lost this antiviral activity in the profit of the IFN pathway is still unclear. We propose that the primary direct antiviral activity of Dicer has been functionally replaced by other sensors in the IFN pathway, leading to its specialization toward microRNA maturation. As a result, Dicer can regulate the innate immune response and prevent basal activation of the IFN pathway in mammals. Here, we discuss this hypothesis, highlighting how the adaptation of the helicase domain of mammalian Dicer may be key to this process.
虽然 Dicer 通过 RNAi 途径在植物和无脊椎动物中发挥重要的抗病毒作用，但它在脊椎动物特别是哺乳动物中的抗病毒免疫作用存在争议。哺乳动物细胞中明显有限的 RNAi 活性归因于哺乳动物 Dicer 的长 dsRNA 连续活性降低，以及 RNAi 和 IFN 途径之间的功能不兼容。为什么 Dicer 在 IFN 途径的利益中失去了这种抗病毒活性仍然不清楚。我们提出，Dicer 的主要直接抗病毒活性已被 IFN 途径中的其他传感器功能替代，导致其专门用于 miRNA 成熟。因此，Dicer 可以调节先天免疫反应并防止哺乳动物中 IFN 途径的基础激活。在这里，我们讨论了这一假设，强调了哺乳动物 Dicer 的解旋酶结构域的适应可能是这一过程的关键。
