A DCL3 Dicing Code Within Pol IV-RDR2 Transcripts Diversifies the SiRNA Pool Guiding RNA-directed DNA Methylation

Overview

Journal Elife

Specialty Biology

Date 2022 Jan 31

PMID 35098919

Authors

Andrew Loffer

Jasleen Singh

Akihito Fukudome

Vibhor Mishra

Feng Wang

Craig S Pikaard

Affiliations

Soon will be listed here.

Abstract

In plants, selfish genetic elements, including retrotransposons and DNA viruses, are transcriptionally silenced by RNA-directed DNA methylation. Guiding the process are short interfering RNAs (siRNAs) cut by DICER-LIKE 3 (DCL3) from double-stranded precursors of ~30 bp that are synthesized by NUCLEAR RNA POLYMERASE IV (Pol IV) and RNA-DEPENDENT RNA POLYMERASE 2 (RDR2). We show that Pol IV's choice of initiating nucleotide, RDR2's initiation 1-2 nt internal to Pol IV transcript ends and RDR2's terminal transferase activity collectively yield a code that influences which precursor end is diced and whether 24 or 23 nt siRNAs are produced. By diversifying the size, sequence, and strand specificity of siRNAs derived from a given precursor, alternative patterns of DCL3 dicing allow for maximal siRNA coverage at methylated target loci.

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References

Tian Y, Simanshu D, Ma J, Park J, Heo I, Kim V . A phosphate-binding pocket within the platform-PAZ-connector helix cassette of human Dicer. Mol Cell. 2014; 53(4):606-16. PMC: 4217634. DOI: 10.1016/j.molcel.2014.01.003. View

Ipsaro J, Joshua-Tor L . From guide to target: molecular insights into eukaryotic RNA-interference machinery. Nat Struct Mol Biol. 2015; 22(1):20-8. PMC: 4450863. DOI: 10.1038/nsmb.2931. View

Law J, Vashisht A, Wohlschlegel J, Jacobsen S . SHH1, a homeodomain protein required for DNA methylation, as well as RDR2, RDM4, and chromatin remodeling factors, associate with RNA polymerase IV. PLoS Genet. 2011; 7(7):e1002195. PMC: 3141008. DOI: 10.1371/journal.pgen.1002195. View

He X, Hsu Y, Zhu S, Wierzbicki A, Pontes O, Pikaard C . An effector of RNA-directed DNA methylation in arabidopsis is an ARGONAUTE 4- and RNA-binding protein. Cell. 2009; 137(3):498-508. PMC: 2700824. DOI: 10.1016/j.cell.2009.04.028. View

Nagano H, Fukudome A, Hiraguri A, Moriyama H, Fukuhara T . Distinct substrate specificities of Arabidopsis DCL3 and DCL4. Nucleic Acids Res. 2013; 42(3):1845-56. PMC: 3919572. DOI: 10.1093/nar/gkt1077. View

Singh J, Mishra V, Wang F, Huang H, Pikaard C . Reaction Mechanisms of Pol IV, RDR2, and DCL3 Drive RNA Channeling in the siRNA-Directed DNA Methylation Pathway. Mol Cell. 2019; 75(3):576-589.e5. PMC: 6698059. DOI: 10.1016/j.molcel.2019.07.008. View

Henderson I, Zhang X, Lu C, Johnson L, Meyers B, Green P . Dissecting Arabidopsis thaliana DICER function in small RNA processing, gene silencing and DNA methylation patterning. Nat Genet. 2006; 38(6):721-5. DOI: 10.1038/ng1804. View

Cao X, Jacobsen S . Role of the arabidopsis DRM methyltransferases in de novo DNA methylation and gene silencing. Curr Biol. 2002; 12(13):1138-44. DOI: 10.1016/s0960-9822(02)00925-9. View

Zhang H, Kolb F, Jaskiewicz L, Westhof E, Filipowicz W . Single processing center models for human Dicer and bacterial RNase III. Cell. 2004; 118(1):57-68. DOI: 10.1016/j.cell.2004.06.017. View

10.

Qi Y, He X, Wang X, Kohany O, Jurka J, Hannon G . Distinct catalytic and non-catalytic roles of ARGONAUTE4 in RNA-directed DNA methylation. Nature. 2006; 443(7114):1008-12. DOI: 10.1038/nature05198. View

11.

Havecker E, Wallbridge L, Hardcastle T, Bush M, Kelly K, Dunn R . The Arabidopsis RNA-directed DNA methylation argonautes functionally diverge based on their expression and interaction with target loci. Plant Cell. 2010; 22(2):321-34. PMC: 2845420. DOI: 10.1105/tpc.109.072199. View

12.

Mosher R, Schwach F, Studholme D, Baulcombe D . PolIVb influences RNA-directed DNA methylation independently of its role in siRNA biogenesis. Proc Natl Acad Sci U S A. 2008; 105(8):3145-50. PMC: 2268599. DOI: 10.1073/pnas.0709632105. View

13.

Mi S, Cai T, Hu Y, Chen Y, Hodges E, Ni F . Sorting of small RNAs into Arabidopsis argonaute complexes is directed by the 5' terminal nucleotide. Cell. 2008; 133(1):116-27. PMC: 2981139. DOI: 10.1016/j.cell.2008.02.034. View

14.

Fukudome A, Singh J, Mishra V, Reddem E, Martinez-Marquez F, Wenzel S . Structure and RNA template requirements of RNA-DEPENDENT RNA POLYMERASE 2. Proc Natl Acad Sci U S A. 2021; 118(51). PMC: 8713982. DOI: 10.1073/pnas.2115899118. View

15.

Matzke M, Mosher R . RNA-directed DNA methylation: an epigenetic pathway of increasing complexity. Nat Rev Genet. 2014; 15(6):394-408. DOI: 10.1038/nrg3683. View

16.

Lahmy S, Pontier D, Bies-Etheve N, Laudie M, Feng S, Jobet E . Evidence for ARGONAUTE4-DNA interactions in RNA-directed DNA methylation in plants. Genes Dev. 2016; 30(23):2565-2570. PMC: 5204349. DOI: 10.1101/gad.289553.116. View

17.

Ream T, Haag J, Wierzbicki A, Nicora C, Norbeck A, Zhu J . Subunit compositions of the RNA-silencing enzymes Pol IV and Pol V reveal their origins as specialized forms of RNA polymerase II. Mol Cell. 2008; 33(2):192-203. PMC: 2946823. DOI: 10.1016/j.molcel.2008.12.015. View

18.

Zhang X, Henderson I, Lu C, Green P, Jacobsen S . Role of RNA polymerase IV in plant small RNA metabolism. Proc Natl Acad Sci U S A. 2007; 104(11):4536-41. PMC: 1810338. DOI: 10.1073/pnas.0611456104. View

19.

Wendte J, Pikaard C . The RNAs of RNA-directed DNA methylation. Biochim Biophys Acta Gene Regul Mech. 2016; 1860(1):140-148. PMC: 5203809. DOI: 10.1016/j.bbagrm.2016.08.004. View

20.

Park J, Heo I, Tian Y, Simanshu D, Chang H, Jee D . Dicer recognizes the 5' end of RNA for efficient and accurate processing. Nature. 2011; 475(7355):201-5. PMC: 4693635. DOI: 10.1038/nature10198. View