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TitleFunctional RNA splitting drove the evolutionary emergence of type V CRISPR-Cas systems from transposons.
Journal, issue, pagesCell, Vol. 188, Issue 22, Page 6283-6300.e22, Year 2025
Publish dateOct 30, 2025
AuthorsShuai Jin / Zixu Zhu / Yunjia Li / Shouyue Zhang / Yijing Liu / Danyuan Li / Yuanqing Li / Yingfeng Luo / Zhiheng Cheng / Kevin Tianmeng Zhao / Qiang Gao / Guanglei Yang / Hongchao Li / Ronghong Liang / Rui Zhang / Jin-Long Qiu / Yong E Zhang / Jun-Jie Gogo Liu / Caixia Gao /
PubMed AbstractTransposon-encoded TnpB nucleases gave rise to type V CRISPR-Cas12 effectors through multiple independent domestication events. These systems use different RNA molecules as guides for DNA targeting: ...Transposon-encoded TnpB nucleases gave rise to type V CRISPR-Cas12 effectors through multiple independent domestication events. These systems use different RNA molecules as guides for DNA targeting: transposon-derived right-end RNAs (reRNAs or omega RNAs) for TnpB and CRISPR RNAs for type V CRISPR-Cas systems. However, the molecular mechanisms bridging transposon activity and CRISPR immunity remain unclear. We identify TranCs (transposon-CRISPR intermediates) derived from distinct IS605- or IS607-TnpB lineages. TranCs utilize both CRISPR RNAs and reRNAs to direct DNA cleavage. The cryoelectron microscopy (cryo-EM) structure of LaTranC from Lawsonibacter sp. closely resembles that of the ISDra2 TnpB complex; however, unlike a single-molecule reRNA, the LaTranC guide RNA is functionally split into a tracrRNA and crRNA. An engineered RNA split of ISDra2 TnpB enabled activity with a CRISPR array. These findings indicate that functional RNA splitting was the primary molecular event driving the emergence of diverse type V CRISPR-Cas systems from transposons.
External linksCell / PubMed:41027434
MethodsEM (single particle)
Resolution2.96 - 3.62 Å
Structure data

61434

9jfo

EMDB-61434, PDB-9jfo:
Structure of LaTranC complex bound to 27nt complementary DNA substrate, conformation 1
Method: EM (single particle) / Resolution: 3.25 Å

61435

9jfp

EMDB-61435, PDB-9jfp:
Structure of LaTranC complex bound to 6nt complementary DNA substrate
Method: EM (single particle) / Resolution: 2.96 Å

61436

9jfq

EMDB-61436, PDB-9jfq:
Structure of LaTranC complex bound to 27nt complementary DNA substrate, conformation 2
Method: EM (single particle) / Resolution: 3.62 Å

Source
  • lawsonibacter sp. (bacteria)
KeywordsIMMUNE SYSTEM/DNA/RNA / LaTranC complexes / IMMUNE SYSTEM-DNA-RNA complex / LaTranC CRISPR RNA complex / DNA / gene editing

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