Home Research Papers RNase κ promotes piRNA production by generating 2′,3′-cyclic phosphate (cP-RNA) precursors

RNase κ promotes piRNA production by generating 2′,3′-cyclic phosphate (cP-RNA) precursors

In our new publication [1], we show that cP-RNAs serve as piRNA precursors in mouse and silkworm. A mitochondria-associated endoribonuclease, BmRNase κ, produces the cP-RNAs and plays an important role in sex determination in silkworms.

In animal germlines, PIWI proteins and the associated PIWI-interacting RNAs (piRNAs) protect genome integrity by silencing transposons. However, even though piRNAs perform this important function, we have not fully identified their biogenesis pathway.

In an attempt to extend our understanding of piRNA biogenesis, we decided to explore the role of cyclic phosphate-containing RNAs (cP-RNAs). In the past, we have developed cP-RNA-seq [2,3], a method that is able to sequence cP-RNAs specifically. We performed cP-RNA-seq, and, here, we report the extensive sequence and quantitative correlations between 2′,3′-cP-RNAs, and piRNAs in the Bombyx germ cell line and mouse teste.

Using P-cP-RNA-seq, we discovered that cP-RNAs containing 5′-phosphate (P-cP-RNAs) harbor highly consistent 5′-end positions. The positions are the same as the mature piRNAs. Additionally, P-cP-RNAs are loaded onto PIWI protein. These suggest the direct utilization of cP-RNAs as piRNA precursors.

Furthermore, we identified Bombyx RNase Kappa (BmRNase κ), a mitochondria-associated endoribonuclease. BmRNase κ produces cP-RNAs during piRNA biogenesis. BmRNase κ -depletion elevated transposon levels and disrupted a piRNA-mediated sex determination in Bombyx embryos, indicating the crucial roles of BmRNase κ in piRNA biogenesis and embryonic development.

Our results reveal a BmRNase κ-engaged piRNA biogenesis pathway, in which the generation of cP-RNAs promotes robust piRNA production.

Our unique RNA-seq method (left panel) revealed RNase κ-engaged piRNA biogenesis pathway, in which the generation of cyclic phosphate-RNAs (cP-RNAs), piRNA precursors, promotes robust piRNA production (right pabel).
Fig 1. Our unique RNA-seq method (left panel) revealed RNase κ-engaged piRNA biogenesis pathway, in which the generation of cyclic phosphate-RNAs (cP-RNAs), piRNA precursors, promotes robust piRNA production (right pabel).

References

  1. Shigematsu M*, Kawamura T*, Morichika K, Izumi N, Kiuchi T, Honda S, Pliatsika V, Matsubara R, Rigoutsos I, Katsuma S, Tomari Y, Kirino Y. RNase κ promotes robust piRNA production by generating 2′,3′-cyclic phosphate-containing precursors. Nat Commun. 2021 Jul 23;12(1):4498. doi: 10.1038/s41467-021-24681-w. PubMed PMID:34301931.
  2. Honda, S, Loher, P, Shigematsu, M, Palazzo, JP, Suzuki, R, Imoto, I, Rigoutsos, I, Kirino, Y. Sex hormone-dependent tRNA halves enhance cell proliferation in breast and prostate cancers. Proc. Natl. Acad. Sci. U.S.A. 2015;112 (29):E3816-25. doi: 10.1073/pnas.1510077112. PubMed PMID:26124144 PubMed Central PMC4517238.
  3. Honda, S, Morichika, K, Kirino, Y. Selective amplification and sequencing of cyclic phosphate-containing RNAs by the cP-RNA-seq method. Nat Protoc. 2016;11 (3):476-89. doi: 10.1038/nprot.2016.025. PubMed PMID:26866791 PubMed Central PMC4852555.

*These authors contributed equally

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