ORC1 binds to cis-transcribed RNAs for efficient activation of replication origins.

Cells must coordinate the activation of thousands of replication origins dispersed throughout their genome. Active transcription is known to favor the formation of mammalian origins, although the role that RNA plays in this process remains unclear. We show that the ORC1 subunit of the human Origin Recognition Complex interacts with RNAs transcribed from genes with origins in their transcription start sites (TSSs), displaying a positive correlation between RNA binding and origin activity. RNA depletion, or the use of ORC1 RNA-binding mutant, result in inefficient activation of proximal origins, linked to impaired ORC1 chromatin release. ORC1 RNA binding activity resides in its intrinsically disordered region, involved in intra- and inter-molecular interactions, regulation by phosphorylation, and phase-separation. We show that RNA binding favors ORC1 chromatin release, by regulating its phosphorylation and subsequent degradation. Our results unveil a non-coding function of RNA as a dynamic component of the chromatin, orchestrating the activation of replication origins.

lncRNA-DNA hybrids regulate distant genes.

lncRNAs actively regulate gene expression. They contribute to chromosomal interactions at close or distant genomic regions, which, in turn, regulate transcription [1]. Ariel et al [2] reveal in a recent study a new molecular mechanism of the Arabidopsis lncRNA APOLO. The authors extend previously reported functions of APOLO in cis-regulation of chromosomal looping and transcription of its neighbor gene to a set of distant genes involved in auxin-induced molecular pathways controlling lateral root development. Noteworthy, APOLO recognition of multiple trans-modulated targets occurs through a novel mechanism involving R-loop formation.