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REVIEW article

Front. Immunol.
Sec. Molecular Innate Immunity
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1451705

Multifunctional Role of DEAD-box Helicase 41 in Innate Immunity, Hematopoiesis and Disease

Provisionally accepted
Jing Ma Jing Ma Susan R. Ross Susan R. Ross *
  • University of Illinois Chicago, Chicago, United States

The final, formatted version of the article will be published soon.

    DEAD-box helicases are multifunctional proteins participating in many aspects of cellular RNA metabolism. DEAD-box helicase 41 (DDX41) in particular has pivotal roles in innate immune sensing and hematopoietic homeostasis. DDX41 recognizes foreign or self-nucleic acids generated during microbial infection, thereby initiating anti-pathogen responses. DDX41 also binds to RNA (R)-loops, structures consisting of DNA/RNA hybrids and a displaced strand of DNA that occur during transcription, thereby maintaining genome stability by preventing their accumulation. DDX41 deficiency leads to increased R-loop levels, resulting in inflammatory responses that likely influence hematopoietic stem and progenitor cell production and development. Beyond nucleic acid binding, DDX41 associates with proteins involved in RNA splicing as well as cellular proteins involved in innate immunity. DDX41 is also a tumor suppressor in familial and sporadic myelodysplastic syndrome/acute myelogenous leukemia (MDS/AML). In the present review, we summarize the functions of DDX helicases in critical biological processes, particularly focusing on DDX41's association with cellular molecules and the mechanisms underlying its roles in innate immunity, hematopoiesis and the development of myeloid malignancies.

    Keywords: DEAD box helicase, Innate immunity, AML/MDS, genomic stability, Splicing

    Received: 19 Jun 2024; Accepted: 18 Jul 2024.

    Copyright: © 2024 Ma and Ross. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Susan R. Ross, University of Illinois Chicago, Chicago, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.