The proposed self-regulation model between the intronic microRNAs (miRNAs) and/or short interfering RNAs (siRNAs) and their host genes. The intronic miRNA/siRNA pathways initiate with the splicing of the primary mRNAs to yield the long- and/or short-hairpin-containing introns, which are the substrates of specific DCLs. Intronic miRNA precursors are processed by coordinated activities of DCL1 and DCL3 to generate canonical miRNAs (cmiRNAs, 21-nt) and long miRNAs (lmiRNAs, 24-nt), respectively. Our analysis based on deep-sequencing data from rice unraveled a strikingly symmetrical distribution of highly abundant siRNA classes, bias to 21, 22, 24 nt in length, diced by DCL4, DCL2, and DCL3, respectively, from the intronic long complementary hairpin precursors. The intronic siRNA pathway, interacting with the intronic miRNA pathway at some level, operates at both chromatin (A) and post-transcriptional levels (B). In A, the intronic 24-nt siRNAs or miRNAs bound to AGO4 proteins interact with nascent transcripts transcribed from their own loci to direct DNA methylation at the adjacent DNA (their host gene loci). Thus, intronic miRNAs/siRNAs control the transcription homeostasis of their host genes by mediating an RNA-directed DNA methylation (RdDM) pathway. Here, we proposed the potential negative correlation between host gene expression and intron-derived siRNA-mediated cis-methylation, which needs to be further validated. In B, the 21-nt siRNAs and miRNAs/miRNAs* are exported to the cytoplasm and then incorporated into AGO1 to carry out the silencing reactions (target mRNA cleavage or translation inhibition).
