Publications

• A Viral Deamidase Targets the Helicase Domain of RIG-I to Block RNA-Induced Activation.

  Zhao J., Zeng Y., Xu S., Chen J., Shen G., Yu C., Knipe D., Yuan W., Peng J., Xu W., Zhang C., Xia Z., Feng P.

  RIG-I detects double-stranded RNA (dsRNA) to trigger antiviral cytokine production. Protein deamidation is emerging as a post-translational modification that chiefly regulates protein function. We report here that UL37 of herpes simplex virus 1 (HSV-1) is a protein deamidase that targets RIG-I to ... >> More

  RIG-I detects double-stranded RNA (dsRNA) to trigger antiviral cytokine production. Protein deamidation is emerging as a post-translational modification that chiefly regulates protein function. We report here that UL37 of herpes simplex virus 1 (HSV-1) is a protein deamidase that targets RIG-I to block RNA-induced activation. Mass spectrometry analysis identified two asparagine residues in the helicase 2i domain of RIG-I that were deamidated upon UL37 expression or HSV-1 infection. Deamidation rendered RIG-I unable to sense viral dsRNA, thus blocking its ability to trigger antiviral immune responses and restrict viral replication. Purified full-length UL37 and its carboxyl-terminal fragment were sufficient to deamidate RIG-I in vitro. Uncoupling RIG-I deamidation from HSV-1 infection, by engineering deamidation-resistant RIG-I or introducing deamidase-deficient UL37 into the HSV-1 genome, restored RIG-I activation and antiviral immune signaling. Our work identifies a viral deamidase and extends the paradigm of deamidation-mediated suppression of innate immunity by microbial pathogens. << Less

  Cell Host Microbe 20:770-784(2016) [PubMed] [EuropePMC]

• Histone H1 deamidation facilitates chromatin relaxation for DNA repair.

  Tian Y., Feng T., Zhang J., Meng Q., Zhan W., Tang M., Liu C., Li M., Tao W., Shu Y., Zhang Y., Chen F., Takeda S., Zhu Q., Lu X., Zhu W.G.

  The formation of accessible chromatin around DNA double-strand breaks is essential for their efficient repair¹. Although the linker histone H1 is known to facilitate higher-order chromatin compaction^2,3, the mechanisms by which H1 modifications regulate chromatin relaxation i ... >> More

  The formation of accessible chromatin around DNA double-strand breaks is essential for their efficient repair¹. Although the linker histone H1 is known to facilitate higher-order chromatin compaction^2,3, the mechanisms by which H1 modifications regulate chromatin relaxation in response to DNA damage are unclear. Here we show that CTP synthase 1 (CTPS1)-catalysed deamidation of H1 asparagine residues 76 and 77 triggers the sequential acetylation of lysine 75 following DNA damage, and this dual modification of H1 is associated with chromatin opening. Mechanistically, the histone acetyltransferase p300 showed a preference for deamidated H1 as a substrate, establishing H1 deamidation as a prerequisite for subsequent acetylation. Moreover, high expression of CTPS1 was associated with resistance to cancer radiotherapy, in both mouse xenograft models and clinical cohorts. These findings provide new insights into how linker histones regulate dynamic chromatin alterations in the DNA damage response. << Less

  Nature 0:0-0(2025) [PubMed] [EuropePMC]