miRNAs in the biogenesis of trans-acting siRNAs in higher plants

Multicellular eukaryotes utilize many complex small RNA mechanisms to regulate gene expression from DNA modifications to RNA stability. RNA interference also regulates exogenous gene expression by degrading invading pathogen RNAs or preventing expression of foreign DNA incorporated into the host genome. Here we review the mechanisms for trans-acting (ta)-siRNA biogenesis and function, including pathways that utilize components of the miRNA and transitive RNAi defense. There are several distinguishing features of ta-siRNA pathways including the requirement for a miRNA-guided cleavage event that sets a processing register, RDR6 dependent dsRNA production, and DCL4 dependent processing to create unique, phased 21 nucleotide small RNAs. These phased small RNAs function to suppress target genes that only show similarity at the ta-siRNA recognition site, and act in trans to repress expression non-cell autonomously of specific target genes. Since the advent of high throughput sequencing technologies, phased siRNAs have been identified in a number of organisms [Heisel SE, Zhang Y, Allen E, Guo L, Reynolds TL, Yang X, et al. Characterization of unique small RNA populations from rice grain. PLoS One 2008;3:e2871. Zhao T, Li G, Mi S, Li S, Hannon GJ, Wang XJ, et al. A complex system of small RNAs in the unicellular green alga Chlamydomonas reinhardtii. Genes Dev 2007;21:1190–203. Johnson C, et al. Clusters and superclusters of phased small RNAs in the developing inflorescence of rice. Genome Res 2009;19:1429–40. Zhu QH, Spriggs A, Matthew L, Fan L, Kennedy G, Gubler F, et al. A diverse set of microRNAs and microRNA-like small RNAs in developing rice grains. Genome Res 2008;18:1456–65. Howell MD, Fahlgren N, Chapman EJ, Cumbie JS, Sullivan CM, Givan SA, et al. Genome-wide analysis of the RNA-DEPENDENT RNA POLYMERASE6/DICER-LIKE4 pathway in Arabidopsis reveals dependency on miRNA- and ta-siRNA-directed targeting. Plant Cell 2007;19:926–42.]. These include transcripts generated either from non-protein-coding or protein-coding transcripts, long imperfect dsRNA or through an unknown mechanism; therefore some of these may not necessarily be classified as canonical ta-siRNAs.