Protein-templated synthesis of dinucleotide repeat DNA by an antiphage reverse transcriptase.
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| Title: | Protein-templated synthesis of dinucleotide repeat DNA by an antiphage reverse transcriptase. |
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| Authors: | Deng, Pujuan (AUTHOR), Lee, Hyunbin (AUTHOR), Armijo, Carlo (AUTHOR), Wang, Haoqing (AUTHOR), Gao, Alex (AUTHOR) |
| Source: | Science. 6/18/2026, Vol. 392 Issue 6804, p1274-1281. 8p. |
| Subjects: | DNA synthesis, Reverse transcriptase, Polymerization, Microsatellite repeats, Non-coding RNA |
| Abstract: | Defense-associated reverse transcriptases (DRTs) are widespread bacterial antiphage systems that use unconventional mechanisms of polynucleotide synthesis. We show that DRT3, which comprises two distinct RTs (Drt3a and Drt3b) and a noncoding RNA (ncRNA), synthesizes alternating poly(GT/AC) double-stranded DNA. Cryo–electron microscopy structures at 2.6-angstrom resolution reveal a D3-symmetric 6:6:6 complex of Drt3a, Drt3b, and ncRNA. Drt3a produces the poly(GT) strand using a conserved ACACAC template within the ncRNA. Notably, Drt3b synthesizes a complementary, protein-primed poly(AC) strand in the complete absence of a nucleic acid template, using conserved active site residues specific to Drt3b to enforce precise base alternation. These findings expand the functional landscape of nucleic acid polymerases, revealing a protein-templated mechanism for sequence-specific DNA synthesis. Editor's summary: Bacterial defense systems often deploy unconventional biochemistry to thwart viral infection. Investigating the antiphage system DRT3, Deng et al. found that it defends against infection by synthesizing repetitive poly(GT/AC) double-stranded DNA using two distinct reverse transcriptases (RTs). One of its RTs copies a noncoding RNA, and the second synthesizes the complementary DNA strand de novo without any nucleic acid template. Instead, it uses its own amino acids as a physical mold to enforce precise base alternation. This work reveals a surprising protein-templated mechanism for sequence-specific DNA synthesis, expanding the known repertoire of enzymatic polymerization. —Di Jiang [ABSTRACT FROM AUTHOR] |
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| Database: | Psychology and Behavioral Sciences Collection |
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| Abstract: | Defense-associated reverse transcriptases (DRTs) are widespread bacterial antiphage systems that use unconventional mechanisms of polynucleotide synthesis. We show that DRT3, which comprises two distinct RTs (Drt3a and Drt3b) and a noncoding RNA (ncRNA), synthesizes alternating poly(GT/AC) double-stranded DNA. Cryo–electron microscopy structures at 2.6-angstrom resolution reveal a D3-symmetric 6:6:6 complex of Drt3a, Drt3b, and ncRNA. Drt3a produces the poly(GT) strand using a conserved ACACAC template within the ncRNA. Notably, Drt3b synthesizes a complementary, protein-primed poly(AC) strand in the complete absence of a nucleic acid template, using conserved active site residues specific to Drt3b to enforce precise base alternation. These findings expand the functional landscape of nucleic acid polymerases, revealing a protein-templated mechanism for sequence-specific DNA synthesis. Editor's summary: Bacterial defense systems often deploy unconventional biochemistry to thwart viral infection. Investigating the antiphage system DRT3, Deng et al. found that it defends against infection by synthesizing repetitive poly(GT/AC) double-stranded DNA using two distinct reverse transcriptases (RTs). One of its RTs copies a noncoding RNA, and the second synthesizes the complementary DNA strand de novo without any nucleic acid template. Instead, it uses its own amino acids as a physical mold to enforce precise base alternation. This work reveals a surprising protein-templated mechanism for sequence-specific DNA synthesis, expanding the known repertoire of enzymatic polymerization. —Di Jiang [ABSTRACT FROM AUTHOR] |
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| ISSN: | 00368075 |
| DOI: | 10.1126/science.aed1656 |
