Mechanism of SiRNA Production from Repetitive DNA

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2015 Feb 19

PMID 25691092

Citations 17

Authors

Qiuying Yang

Qiaohong Anne Ye

Yi Liu

Affiliations

Soon will be listed here.

Abstract

RNAi is a conserved genome defense mechanism in eukaryotes that protects against deleterious effects of transposons and viral invasion. Repetitive DNA loci are a major source for the production of eukaryotic small RNAs, but how these small RNAs are produced is not clear. Quelling in Neurospora is one of the first known RNAi-related phenomena and is triggered by the presence of multiple copies of transgenes. Here we showed that DNA tandem repeats and double-strand breaks are necessary and, when both are present, sufficient to trigger gene silencing and siRNA production. Introduction of a site-specific double-strand break or DNA fragile site resulted in homologous recombination of repetitive sequences, which is required for gene silencing. In addition to siRNA production, the quelling pathway also maintains tandem repeats by regulating homologous recombination. Our study identified the mechanistic trigger for siRNA production from repetitive DNA and established a role for siRNA in maintaining genome stability.

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References

Ishibashi K, Suzuki K, Ando Y, Takakura C, Inoue H . Nonhomologous chromosomal integration of foreign DNA is completely dependent on MUS-53 (human Lig4 homolog) in Neurospora. Proc Natl Acad Sci U S A. 2006; 103(40):14871-6. PMC: 1595443. DOI: 10.1073/pnas.0604477103. View

Jarem D, Huckaby L, Delaney S . AGG interruptions in (CGG)(n) DNA repeat tracts modulate the structure and thermodynamics of non-B conformations in vitro. Biochemistry. 2010; 49(32):6826-37. PMC: 3650493. DOI: 10.1021/bi1007782. View

Cogoni C, Macino G . Posttranscriptional gene silencing in Neurospora by a RecQ DNA helicase. Science. 1999; 286(5448):2342-4. DOI: 10.1126/science.286.5448.2342. View

Lee H, Chang S, Choudhary S, Aalto A, Maiti M, Bamford D . qiRNA is a new type of small interfering RNA induced by DNA damage. Nature. 2009; 459(7244):274-7. PMC: 2859615. DOI: 10.1038/nature08041. View

Francia S, Michelini F, Saxena A, Tang D, de Hoon M, Anelli V . Site-specific DICER and DROSHA RNA products control the DNA-damage response. Nature. 2012; 488(7410):231-5. PMC: 3442236. DOI: 10.1038/nature11179. View

Eichler E, Holden J, Popovich B, Reiss A, Snow K, Thibodeau S . Length of uninterrupted CGG repeats determines instability in the FMR1 gene. Nat Genet. 1994; 8(1):88-94. DOI: 10.1038/ng0994-88. View

Ghildiyal M, Zamore P . Small silencing RNAs: an expanding universe. Nat Rev Genet. 2009; 10(2):94-108. PMC: 2724769. DOI: 10.1038/nrg2504. View

Lee H, Aalto A, Yang Q, Chang S, Huang G, Fisher D . The DNA/RNA-dependent RNA polymerase QDE-1 generates aberrant RNA and dsRNA for RNAi in a process requiring replication protein A and a DNA helicase. PLoS Biol. 2010; 8(10). PMC: 2950127. DOI: 10.1371/journal.pbio.1000496. View

Wang X, Hsueh Y, Li W, Floyd A, Skalsky R, Heitman J . Sex-induced silencing defends the genome of Cryptococcus neoformans via RNAi. Genes Dev. 2010; 24(22):2566-82. PMC: 2975932. DOI: 10.1101/gad.1970910. View

10.

Freitag M, Lee D, Kothe G, Pratt R, Aramayo R, Selker E . DNA methylation is independent of RNA interference in Neurospora. Science. 2004; 304(5679):1939. DOI: 10.1126/science.1099709. View

11.

Samadashwily G, Raca G, Mirkin S . Trinucleotide repeats affect DNA replication in vivo. Nat Genet. 1997; 17(3):298-304. DOI: 10.1038/ng1197-298. View

12.

Zhang Z, Chang S, Zhang Z, Xue Z, Zhang H, Li S . Homologous recombination as a mechanism to recognize repetitive DNA sequences in an RNAi pathway. Genes Dev. 2013; 27(2):145-50. PMC: 3566306. DOI: 10.1101/gad.209494.112. View

13.

Romano N, Macino G . Quelling: transient inactivation of gene expression in Neurospora crassa by transformation with homologous sequences. Mol Microbiol. 1992; 6(22):3343-53. DOI: 10.1111/j.1365-2958.1992.tb02202.x. View

14.

Chicas A, Cogoni C, Macino G . RNAi-dependent and RNAi-independent mechanisms contribute to the silencing of RIPed sequences in Neurospora crassa. Nucleic Acids Res. 2004; 32(14):4237-43. PMC: 514385. DOI: 10.1093/nar/gkh764. View

15.

Nolan T, Braccini L, Azzalin G, De Toni A, Macino G, Cogoni C . The post-transcriptional gene silencing machinery functions independently of DNA methylation to repress a LINE1-like retrotransposon in Neurospora crassa. Nucleic Acids Res. 2005; 33(5):1564-73. PMC: 1065258. DOI: 10.1093/nar/gki300. View

16.

Siomi M, Saito K, Siomi H . How selfish retrotransposons are silenced in Drosophila germline and somatic cells. FEBS Lett. 2008; 582(17):2473-8. DOI: 10.1016/j.febslet.2008.06.018. View

17.

Napoli C, Lemieux C, Jorgensen R . Introduction of a Chimeric Chalcone Synthase Gene into Petunia Results in Reversible Co-Suppression of Homologous Genes in trans. Plant Cell. 1990; 2(4):279-289. PMC: 159885. DOI: 10.1105/tpc.2.4.279. View

18.

Pendyala L, Wellman A . Effect of histidine on purine nucleotide synthesis and utilization in Neurospora crassa. J Bacteriol. 1975; 124(1):78-85. PMC: 235867. DOI: 10.1128/jb.124.1.78-85.1975. View

19.

Chicas A, Forrest E, Sepich S, Cogoni C, Macino G . Small interfering RNAs that trigger posttranscriptional gene silencing are not required for the histone H3 Lys9 methylation necessary for transgenic tandem repeat stabilization in Neurospora crassa. Mol Cell Biol. 2005; 25(9):3793-801. PMC: 1084287. DOI: 10.1128/MCB.25.9.3793-3801.2005. View

20.

Goldoni M, Azzalin G, Macino G, Cogoni C . Efficient gene silencing by expression of double stranded RNA in Neurospora crassa. Fungal Genet Biol. 2004; 41(11):1016-24. DOI: 10.1016/j.fgb.2004.08.002. View