title: Non-coding Y RNAs associate with early replicating euchromatin in concordance with the origin recognition complex.
abstract: Non-coding Y RNAs are essential for the initiation of chromosomal DNA replication in vertebrates, yet their association with chromatin during the cell cycle is not characterised. Here, we quantify human Y RNA levels in soluble and chromatin-associated intracellular fractions and investigate, topographically, their dynamic association with chromatin during the cell cycle. We find that, on average, about a million Y RNA molecules are present in the soluble fraction of a proliferating cell, and 5-10-fold less are in association with chromatin. These levels decrease substantially during quiescence. No significant differences are apparent between cancer and non-cancer cell lines. Y RNAs associate with euchromatin throughout the cell cycle. Their levels are 2-4-fold higher in S phase than in G1 phase or mitosis. Y RNAs are not detectable at active DNA replication foci, and re-associate with replicated euchromatin during mid and late S phase. The dynamics and sites of Y1 RNA association with chromatin are in concordance with those of the origin recognition complex (ORC). Our data therefore suggest a functional role of Y RNAs in a common pathway with ORC.
authors.affiliation: Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK.
authors.forename: Eyemen
authors.initials: E
authors.lastname: Kheir
authors.affiliation: Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK tk218@cam.ac.uk.
authors.forename: Torsten
authors.identifier: 0000-0002-1842-1933
authors.initials: T
authors.lastname: Krude
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004261:DNA Replication / Q000235:genetics*; D022041:Euchromatin / Q000378:metabolism*; D016193:G1 Phase; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000473:pathology; D051738:Origin Recognition Complex / Q000235:genetics*; D022661:RNA, Untranslated / Q000235:genetics*; D016196:S Phase
chemical_list: D022041:Euchromatin; D051738:Origin Recognition Complex; D022661:RNA, Untranslated
keywords: Cell cycle; Chromatin association; DNA replication; Initiation; Non-coding Y RNA; ORC; Origin recognition complex