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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE173452 | GEO | 2023/06/05

REPOSITORIES: GEO

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

Project description: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.

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ORC1 binds to cis-transcribed RNAs for efficient activation of human origins [SNSseq]

Project description:By investigating the RNA binding activity of human ORC1, we show that it interacts with RNAs transcribed at active origins, which is linked to ORC1 dynamic association to the chromatin and optimal origin firing in S phase.

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