RNA interference (RNAi) is a cellular process known for inhibiting gene expression in a sequence-specific manner. In the fission yeast Schizosaccharomyces pombe, this process induces modifications in chromatin structure and is assumed to involve an interaction between nascent transcripts and a small RNA contained in the RNAi complex, RITS (RNA-induced Initiation of Transcriptional gene Silencing). RITS targets repeated and non-coding regions, and is essential for heterochromatin integrity at these genomic sites. In one study, RITS complex subunit Argonaute 1, and a heterochromatin mark, methylation of histone H3 on lysine 9 (H3K9me), were detected on chromatin of two meiotic genes, mei4 and ssm4. This finding suggested a possible new function for RNAi in sexual differentiation. During my PhD studies, I found that a RNA-binding protein, Mmi1 (Meiotic mRNA interception protein 1), enables RITS to specifically associate with the chromatin and messenger RNAs of these meiotic genes. Mmi1 protein triggers a post-transcriptional repression of specific meiotic genes, a silencing activity essential for the control of sexual differentiation. We conducted a genome wide transcriptomic analysis from a mmi1Δ strain, and uncovered additional meiotic mRNAs that are directly targeted by both Mmi1 and RNAi. Intriguingly, chromatin of the corresponding meiotic genes does not necessarily display the repressive epigenetic mark H3K9me, suggesting that RNAi might silence some protein-coding genes only at a post-transcriptional level. In parallel, combining genetic, molecular biology and physiological techniques, we highlighted a potentially direct role for RNAi in the inhibition of sexual differentiation. We propose that RNAi cooperates with Mmi1 to efficiently block expression of the early meiotic transcriptional programme during vegetative growth. This regulation might be essential for the proper timing of activation of this programme during sexual differentiation progression.
