美国科罗拉多大学Edward B. Chuong研究小组发现，转座子外显子化调控人类干扰素信号通路。这一研究成果于2024年12月12日在线发表在国际学术期刊《细胞》上。

研究人员发现来源于转座子外显子的可变剪接是调控人类细胞免疫信号的关键机制。通过分析长读长转录组数据集，研究人员鉴定出多个转座子外显子化事件，预计这些事件将产生免疫基因的功能性蛋白变体，包括I型干扰素受体IFNAR2。

研究人员证明了，IFNAR2的转座子来源亚型在几乎所有组织中都比经典亚型更高表达，并且作为诱饵受体，强效抑制干扰素信号，包括在严重急性呼吸综合症冠状病毒2型（SARS-CoV-2）感染的细胞中。该研究揭示了一种灵长类特有的信号轴来控制干扰素信号，并展示了转座子外显子化事件如何被用来调节免疫反应。

据了解，先天免疫信号对于清除病原体和损伤细胞至关重要，必须严格调控以避免过度炎症或自身免疫反应。

附：英文原文

Title: Regulation of human interferon signaling by transposon exonization

Author: Giulia Irene Maria Pasquesi, Holly Allen, Atma Ivancevic, Arturo Barbachano-Guerrero, Olivia Joyner, Kejun Guo, David M. Simpson, Keala Gapin, Isabella Horton, Lily L. Nguyen, Qing Yang, Cody J. Warren, Liliana D. Florea, Benjamin G. Bitler, Mario L. Santiago, Sara L. Sawyer, Edward B. Chuong

Issue&Volume: 2024-12-12

Abstract: Innate immune signaling is essential for clearing pathogens and damaged cells and must be tightly regulated to avoid excessive inflammation or autoimmunity. Here, we found that the alternative splicing of exons derived from transposable elements is a key mechanism controlling immune signaling in human cells. By analyzing long-read transcriptome datasets, we identified numerous transposon exonization events predicted to generate functional protein variants of immune genes, including the type I interferon receptor IFNAR2. We demonstrated that the transposon-derived isoform of IFNAR2 is more highly expressed than the canonical isoform in almost all tissues and functions as a decoy receptor that potently inhibits interferon signaling, including in cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our findings uncover a primate-specific axis controlling interferon signaling and show how a transposon exonization event can be co-opted for immune regulation.

DOI: 10.1016/j.cell.2024.11.016

Source: https://www.cell.com/cell/abstract/S0092-8674(24)01333-3