Blocking RAN translation without altering repeat RNAs rescues C9ORF72-related ALS and FTD phenotypes - Science | AAAS

Chimeric RNAs (chRNAs) expand transcriptomic and proteomic diversity by joining sequences from distinct genomic loci, yet their physiological functions remain poorly understood. In a recent paper published in Nature, Venezia et al. show that inflammation induces CTCF-dependent chRNA formation in mammalian immune cells and that a Gsdmd-Tmem106a chRNA encodes a functional fusion protein that modulates pyroptosis and the balance between antibacterial defense and inflammatory pathology. The mammalian genome contains a surprisingly limited number of protein-coding genes relative to the complexity of mammalian organisms. Alternative splicing, RNA editing, non-canonical translation and post-translational modification expand the functional output of this finite genome. Chimeric RNAs (chRNAs), in which sequences from distinct genomic loci are joined within a single transcript, may represent another layer of this regulatory complexity.1,2,3 Historically, chimeric transcripts have been closely associated with cancer-associated chromosomal rearrangements.