MiCEE: a ncRNA-protein complex mediates epigenetic silencing and nucleolus organization

The majority of the eukaryotic genome is transcribed into non-coding RNAs (ncRNAs), which are important regulators of different biological processes in the cell nucleus as part of the machinery controlling chromatin structure. However, the full extent of ncRNAs function has remained elusive. Here we deciphered the function of the microRNA Mirlet7d as a key regulator of the expression of bi-directionally transcribed genes. We found that nuclear Mirlet7d binds ncRNAs expressed from these genes. The Mirlet7d-ncRNA duplexes are further bound by C1D, which in turn targets the RNA exosome complex and EZH2 to the bi-directionally active loci. The exosome degrades the ncRNAs, whereas EZH2 induces heterochromatin and transcriptional silencing. Moreover, this multicomponent RNA-protein complex, which we called MiCEE, tethers the regulated genes to the perinucleolar region, thereby being required for proper nucleolus organization. Our study demonstrates that the MiCEE complex mediates epigenetic silencing of bi-directionally expressed genes and global genome organization. RNA_Seq Data from MLE-12 cells: i) Investigate the effect of Mirlet7d gain-of-function on the RNA population in the nucleus of the cell. ii) Pulldown experiment to identify the RNAs that interact with Mirlet7d in the nucleus of the cell. RNA-seq after Mirlet7d-Pulldown, RNA-seq after Mirlet7d-GOF, Mirlet7d-ChIRP-seq and small_RNA_Seq from MLE-12 cells