维尔纽斯堡大学Martin Eilers团队近日取得一项新成果。经过不懈努力，他们的研究认为MYC与新生RNA的结合通过R-环衍生的RNA-DNA杂交抑制先天免疫信号传导。2026年1月22日出版的《细胞》发表了这项成果。
该课题组证明MYC在内含子RNA积累后从DNA上的规范位置全局重新定位到新生RNA。与RNA结合后，MYC形成多聚体，将核外泌体（RNA外切酶）及其靶向复合物集中在双链RNA和R环周围。MYC含有它们的RNA结合区（RBRI-IV）。RBRIII促进MYC多化，是将外泌体招募到R环所必需的。RBRIII对于胰腺肿瘤细胞的转录激活和培养增殖是必不可少的，但对于维持肿瘤在体内的生长是必不可少的。MYC通过RBRIII抑制R环衍生的RNA-DNA杂交体的积累，并通过TLR3模式识别受体阻止它们激活先天免疫激酶TBK1。他们的数据表明，MYC的相变是一种RNA驱动的应激反应，抑制了免疫原性RNA-DNA杂交体的积累。
研究人员表示，在转录伸长受到干扰的情况下，MYC癌蛋白聚合并经历一个相变。
附：英文原文
Title: MYC binding to nascent RNA suppresses innate immune signaling by R-loop-derived RNA-DNA hybrids
Author: Leonie Uhl, Amel Aziba, Sinah Lbbert, Timothy Russell, Bastian Krenz, Francisco Montesinos, Toshitha Kannan, Omkar R. Valanju, Christina Schülein-Vlk, Tim de Martines, Michael Bolz, Daniel Fleischhauer, Giacomo Cossa, Theresa Endres, Daniel Solvie, Peter Gallant, Andreas Rosenwald, Hans M. Maric, Dimitrios Papadopoulos, Seychelle M. Vos, Martin Eilers
Issue&Volume: 2026-01-22
Abstract: In response to perturbed transcription elongation, the MYC oncoprotein multimerizes and undergoes a phase transition. Here, we demonstrate that MYC globally relocalizes from its canonical positions on DNA to nascent RNA upon accumulation of intronic RNA. Upon binding to RNA, MYC forms multimers that concentrate the nuclear exosome, an RNA exonuclease, and its targeting complexes around double-stranded RNA and R-loops. MYC harbors four RNA-binding regions (RBRI–IV). RBRIII promotes MYC multimerization and is necessary for recruiting the exosome to R-loops. RBRIII is dispensable for transcriptional activation and pancreatic tumor cell proliferation in culture, but it is indispensable for sustaining tumor growth in vivo. Via RBRIII, MYC suppresses the accumulation of R-loop-derived RNA-DNA hybrids and prevents them from activating the innate immune kinase TBK1 via the TLR3 pattern recognition receptor. Our data demonstrate that the phase transition of MYC is an RNA-driven stress response that suppresses the accumulation of immunogenic RNA-DNA hybrids.
DOI: 10.1016/j.cell.2025.12.019
Source: https://www.cell.com/cell/abstract/S0092-8674(25)01432-1