SAMHD1 controls innate immunity by regulating condensation of immunogenic self RNA

Research output: Contribution to journalResearch articleContributedpeer-review


  • Shovamayee Maharana - , Chair of Cellular Biochemistry, Indian Institute of Science Bangalore (Author)
  • Stefanie Kretschmer - , Department of Paediatrics (Author)
  • Susan Hunger - , Department of Child and Adolescent Psychiatry and Psychotherapy (Author)
  • Xiao Yan - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • David Kuster - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Sofia Traikov - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Thomas Zillinger - , University of Bonn (Author)
  • Marc Gentzel - , Core Facility Mass Spectrometry & Proteomics (Author)
  • Shobha Elangovan - , Indian Institute of Science Bangalore (Author)
  • Padmanava Dasgupta - , Indian Institute of Science Bangalore (Author)
  • Nagaraja Chappidi - , Chair of Cellular Biochemistry (Author)
  • Nadja Lucas - , Department of Paediatrics (Author)
  • Katharina Isabell Maser - , University of Bonn (Author)
  • Henrike Maatz - , Max Delbrück Center for Molecular Medicine (MDC) (Author)
  • Alexander Rapp - , Technische Universität Darmstadt (Author)
  • Virginie Marchand - , Université de Lorraine (Author)
  • Young Tae Chang - , Pohang University of Science and Technology (Author)
  • Yuri Motorin - , Université de Lorraine (Author)
  • Norbert Hubner - , Max Delbrück Center for Molecular Medicine (MDC), Charité – Universitätsmedizin Berlin, Deutsches Zentrum für Herz-Kreislaufforschung (DZHK) (Author)
  • Gunther Hartmann - , University of Bonn (Author)
  • Anthony A. Hyman - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Simon Alberti - , Biotechnology Center, Chair of Cellular Biochemistry (Author)
  • Min Ae Lee-Kirsch - , Department of Paediatrics (Author)


Recognition of pathogen-derived foreign nucleic acids is central to innate immune defense. This requires discrimination between structurally highly similar self and nonself nucleic acids to avoid aberrant inflammatory responses as in the autoinflammatory disorder Aicardi-Goutières syndrome (AGS). How vast amounts of self RNA are shielded from immune recognition to prevent autoinflammation is not fully understood. Here, we show that human SAM-domain- and HD-domain-containing protein 1 (SAMHD1), one of the AGS-causing genes, functions as a single-stranded RNA (ssRNA) 3′exonuclease, the lack of which causes cellular RNA accumulation. Increased ssRNA in cells leads to dissolution of RNA-protein condensates, which sequester immunogenic double-stranded RNA (dsRNA). Release of sequestered dsRNA from condensates triggers activation of antiviral type I interferon via retinoic-acid-inducible gene I-like receptors. Our results establish SAMHD1 as a key regulator of cellular RNA homeostasis and demonstrate that buffering of immunogenic self RNA by condensates regulates innate immune responses.


Original languageEnglish
Pages (from-to)3712-3728.e1-e10
Number of pages28
JournalMolecular cell
Issue number19
Publication statusPublished - 6 Oct 2022

External IDs

PubMed 36150385
WOS 000898432000004
ORCID /0000-0002-4482-6010/work/142251013
ORCID /0000-0003-4017-6505/work/142253848


Research priority areas of TU Dresden

DFG Classification of Subject Areas according to Review Boards

Sustainable Development Goals


  • Aicardi-Goutières syndrome, autoinflammation, condensate, dsRNA, innate immunity, phase separation, RNA, SAMHD1, stress granules, type I interferon, SAM Domain and HD Domain-Containing Protein 1/genetics, Humans, Nervous System Malformations, Antiviral Agents, Immunity, Innate/genetics, Autoimmune Diseases of the Nervous System, Interferon Type I/genetics, Exonucleases/genetics, RNA, Double-Stranded/genetics, Separation, Triphosphate, Inhibition, Double-stranded-rna, Acid binding-protein, Phase-transition, Restriction factor samhd1, Aicardi-goutieres syndrome, Hiv-1 restriction, Recognition