Figure 6. Model for Mmi1/exosome YTH-mediated control of cell differentiation and heterochromatin gene silencing mediated by its targeting of nascent lncRNA and the induction of their transcription termination. The YTH domain of Mmi1 co-transcriptionally binds to specific lncRNAs expressed from either euchromatin or heterochromatin regions. We propose that Mmi1 binding to a euchromatic nascent lncRNA (in green) induces the recruitment of the exosome and together they degrade the lncRNA and promote robust termination of the lncRNA transcription, which otherwise will inhibit the expression of the downstream protein-coding gene (in blue). In the case of nam1-byr2 locus, the efficient transcription termination prevents the occurrence of read-through transcription from nam1 gene, which represses byr2 MAPKKK gene, a critical regulator of the entry into sexual differentiation. In parallel, Mmi1 co-transcriptional binding to the heterochromatic pericentromeric lncRNAs also recruits the exosome and contributes to heterochromatin gene silencing by degrading the nascent lncRNAs as well as by inducing precocious termination of their transcription. STOP sign, site of Mmi1-dependent lncRNA transcription termination. 