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Abstract Upon sensing cytosolic- and/or viral double-stranded (ds)DNA, absent-in-melanoma-2 (AIM2)-like-receptors (ALRs) assemble into filamentous signaling platforms to initiate inflammatory responses. The versatile yet critical roles of ALRs in host innate defense are increasingly appreciated; however, the mechanisms by which AIM2 and its related IFI16 specifically recognize dsDNA over other nucleic acids remain poorly understood (i.e. single-stranded (ss)DNA, dsRNA, ssRNA and DNA:RNA hybrid). Here, we find that although AIM2 can interact with various nucleic acids, it preferentially binds to and assembles filaments faster on dsDNA in a duplex length-dependent manner. Moreover, AIM2 oligomers assembled on nucleic acids other than dsDNA not only display less ordered filamentous structures, but also fail to induce the polymerization of downstream ASC. Likewise, although showing broader nucleic acid selectivity than AIM2, IFI16 binds to and oligomerizes most readily on dsDNA in a duplex length-dependent manner. Nevertheless, IFI16 fails to form filaments on single-stranded nucleic acids and does not accelerate the polymerization of ASC regardless of bound nucleic acids. Together, we reveal that filament assembly is integral to nucleic acid distinction by ALRs.
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Synthetic approaches for copolymers containing nucleic acids and analogues: challenges and opportunities
Deep integration of nucleic acids with other classes of materials has become the basis of many useful technologies. Among these biohybrids, nucleic acid-containing copolymers have seen rapid development in both chemistry and applications. This review focuses on the various synthetic approaches for accessing nucleic acid–polymer biohybrids spanning post-polymerization conjugation, nucleic acids in polymerization, solid-phase synthesis, and nucleoside/nucleobase-functionalized polymers. We highlight the challenges associated with working with nucleic acids with each approach and the ingenuity of the solutions, with the hope of lowering the entry barrier and inspiring further investigations in this exciting area.
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- Award ID(s):
- 2004947
- PAR ID:
- 10225738
- Date Published:
- Journal Name:
- Polymer Chemistry
- Volume:
- 12
- Issue:
- 15
- ISSN:
- 1759-9954
- Page Range / eLocation ID:
- 2193 to 2204
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/d0py01707h
