On May 1, 2025, the Jia Ning team from Southern University of Science and Technology published an article in Science, achieving significant results in the field of phage research. She obtained her PhD fromUniversity of Science and Technology of China, School of Life Sciences (supervisors: Professors Zhou Congzhao and Chen Yuxing), and completed her undergraduate studies at Ocean University of China.

Recently, Associate Professor Jia Ning’s research team at the School of Medicine of Southern University of Science and Technology published two significant research papers in Science within a week, revealing the novel working mechanisms of key reverse transcriptases (DRTs) and RNA-mediated CRISPR-Cas inhibitory factors in bacterial defense mechanisms.

DRT9: Using Long Poly-A Enriched cDNA to Resist Phages

On May 1, 2025, the Jia Ning team published a research paper titled “Bacterial reverse transcriptase synthesizes long poly-A–rich cDNA for antiphage defense” in Science, systematically elucidating how the newly discovered defense-related reverse transcriptase DRT9 utilizes its unique structural and functional mechanisms to achieve immune defense against phages. This study reveals for the first time that DRT9 can synthesize long poly-A enriched single-stranded cDNA under high concentrations of dATP, which can directly bind to and chelate the single-stranded DNA binding protein (SSB) of phage T4, thereby interfering with the DNA replication of the phage.

In this study, researchers found that the phage resistance activity of DRT9 is highly dependent on its interaction with non-coding RNA (ncRNA). The complex formed by DRT9 and ncRNA can synthesize long poly-A enriched single-stranded cDNA in the presence of high concentrations of dATP, which is achieved through the conserved catalytic YADD motif of DRT9. When ncRNA is absent or the YADD motif is mutated, the phage resistance activity of DRT9 is almost completely lost.

Cryo-electron microscopy structural analysis shows that the DRT9-ncRNA complex assembles into a stable hexamer in the form of a “dimeric trimer,” where ncRNA interacts with DRT9 through multiple stem-loop structures (SLs), further stabilizing the overall conformation of the hexamer. The stability of this complex structure is fundamental to the phage resistance function of DRT9.

Furthermore, the study also found that phages can evade the DRT9-mediated immune response by regulating the host’s dATP levels. When wild-type phages infect, the intracellular dATP levels significantly increase, activating the DRT9 system; however, when the phage’s NrdB gene is mutated, leading to restricted dATP production, the defense mechanism of DRT9 fails. This indicates that phages can evade DRT9-mediated immunity by modulating the intracellular dATP levels of host cells.

This research not only reveals a novel defense mechanism involving DRT9 but also provides an important structural basis for the future development of antiviral tools based on DRT9.

RNA Structural Mimicry Inhibits CRISPR-Cas13 Activity

In addition to the DRT9 research, the Jia Ning team also collaborated with the Alexander J. Meeske team from the University of Washington on April 24, 2025, to publish a back-to-back study titled “RNA-mediated CRISPR-Cas13 inhibition through crRNA structural mimicry” in Science, revealing how small RNA anti-CRISPR factors (rAcrs) inhibit the activity of the CRISPR-Cas system through RNA structural mimicry.

This paper focuses on the CRISPR-Cas13 system, a type of RNA-targeting nuclease system widely found in bacteria, which can defend against viruses and plasmids by cleaving RNA. However, phages have evolved various Acrs to evade this immune attack. Although most Acrs are proteins, the recently discovered rAcrs have opened a new research direction.

In this study, researchers identified a small RNA molecule named rAcrVIA1, which, despite having almost no sequence similarity to CRISPR RNA (crRNA), has a spatial structure highly similar to crRNA. Through cryo-electron microscopy analysis, researchers revealed that rAcrVIA1 forms two stem-loop structures (SL1 and SL2) that can bind to Cas13 and prevent it from recognizing and cleaving target RNA.

More importantly, the study also found that the expression of rAcrVIA1 is regulated by its upstream orf1 gene. The protein encoded by orf1 can inhibit the activity of its own promoter Porf1; when the orf1 gene is knocked out or the -10 element of its promoter Porf1 is mutated, the expression of rAcrVIA1 significantly decreases. This indicates that orf1 indirectly regulates the expression of rAcrVIA1 by inhibiting the transcriptional activity of Porf1.

This finding not only expands the diversity of rAcrs but also provides new insights into the evolutionary interplay between bacteria and phages in immune and counter-immune strategies.

About Jia Ning

Jia Ning is an Associate Professor at the School of Medicine of Southern University of Science and Technology and a PhD supervisor. In 2022, she was selected for the “35 Innovators Under 35” Asia-Pacific list by MIT Technology Review, and in 2020, she received the Blavatnik Regional Young Scientist Award in Chemistry. In 2024, she became a member of the Editorial Board of the Journal of Biological Chemistry (JBC).

Jia Ning obtained her PhD from the University of Science and Technology of China in 2016 and conducted postdoctoral research at the Memorial Sloan Kettering Cancer Center in the United States from 2017 to 2021, under the supervision of Academician Dinshaw J. Patel. In 2021, she joined the School of Medicine at Southern University of Science and Technology, with primary research interests in the molecular mechanisms of interactions between microorganisms and the host immune system. In recent years, she has published several high-level papers as a corresponding author in journals such as Nature Chemical Biology, Molecular Cell, Nature Communications, and Science.

Editor and Reviewer: Da Ke

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