m6A-modified exosome-derived circHIF1α binding to KH domain of IGF2BP3 mediates DNA damage and arrests G1/S transition phase to resists bacterial infection in bacteremia
We first discovered a new circHIF1α that was very stable and detectable, encapsulated into exosomes by hnRNPA2B1, and whose expression in exosomes of bacterially infected PIEC cells significantly decreased. Additionally, exosomal circHIF1α reduced bacterial infection both in vitro and in vivo and suppressed the growth of reception cells. Mechanistically, the circHIF1α interacted with the KH domain of IGF2BP3 in an m6A-modified manner, which mediated DNA damage to arrest the cells at the G1/S phase through the interaction between the regulator of Chromosome Condensation 2 (RCC2) and γ-H2AX protein. Exosomal circHIF1α is a unique therapeutic target for bacterial infection since this work highlights its critical function in fighting bacterial infection.
Authors
- Fei Liu (ORCID: https://orcid.org/0000-0002-0926-5588)
- Jiang Yu (ORCID: https://orcid.org/0000-0002-7550-5041)
- Jie Yang (ORCID: https://orcid.org/0000-0003-3469-5931)
- Wenbo Sun (ORCID: https://orcid.org/0000-0002-5301-4938)
- Jian Jiao (ORCID: https://orcid.org/0000-0002-7988-9820)
- Jianda Li (ORCID: https://orcid.org/0000-0001-5453-5420)
- Jiaqiang Wu (ORCID: https://orcid.org/0000-0001-9160-9951)
- Luo‐Gang Ding
- Zhi Chen (ORCID: https://orcid.org/0000-0002-0848-1502)
- Yuyu Zhang (ORCID: https://orcid.org/0000-0003-3095-3083)
- Yidan Gao (ORCID: https://orcid.org/0009-0000-7822-5953)
- Feng Gong (ORCID: https://orcid.org/0000-0001-5953-3571)
- Sufang Ren
Institutions
- Shandong Normal University (CN)
- Shandong Academy of Agricultural Sciences (CN)
Publication Details
- Journal
- Journal of Nanobiotechnology
- Published
- 2024-10-24
- DOI
- https://doi.org/10.1186/s12951-024-02932-4
- Citations
- 6
- Primary Topic
- RNA modifications and cancer
- Type
- article
- Field-Weighted Citation Impact
- 1.40
Funders
- National Key Research and Development Program of China