Fig. 1: RNA processing mechanisms contributing to genome organization and stability.

Eukaryotic genome and chromatin organization are influenced by ncRNAs and RNA processing actors, including 5’ exoribonucleases, endoribonucleases, 3’ exoribonucleases, RNA helicases, RNA-modifying enzymes, and RNA-binding proteins, amongst others. RNA helicases and ribonucleases are particularly important to unwind RNAs and DNA-associated RNAs and ultimately to degrade them. A NcRNAs influence chromatin epigenetic states by facilitating the recruitment of histone- and DNA-modifying enzymes such as Polycomb repressive complex or DNA methyltransferases, respectively. RNA processing mechanisms regulate these ncRNAs and thus influence chromatin states. In parallel, RNA-modifying enzymes can catalyse (writer) RNA chemical modifications, such as m6A, remove them (eraser) and bind to them (reader). These RNA modifications modulate the half-life and associated biological activities of different types of RNA transcripts. B Transcription can create DNA-associated RNAs, forming R-loops, that are processed by various mechanisms to prevent their deleterious effects on genome stability, such as DNA mutations and double-strand breaks. Ribonucleotides incorporated into DNA also threaten genome integrity and are processed, notably by RNase H. C DNA-damage response RNAs (ddRNAs) can be produced after DNA breaks, either facilitating or inhibiting DNA repair by HR or NHEJ. RNA processing pathways contribute to ddRNA regulation and successful DNA repair. D Left. The mechanism of loop extrusion relies on the architectural proteins CTCF and cohesin. CTCF proteins directly bind to the DNA while the cohesin complex extrudes DNA to create DNA loops and TADs. Right. The binding of CTCF to the chromatin is dependent on its RNA-binding domain, ncRNAs are produced at CTCF-binding elements and are processed by RNA helicases and the RNA exosome, while cohesin scanning is slowed down by DNA:RNA hybrid accumulation.