MRC National Institute for Medical Research, London
Science for Health
The onset of Y RNA-dependent DNA replication in Xenopus laevis
04 August 2011
Scientists at NIMR in collaboration with the Gurdon Institute and the Zoology Department in Cambridge have shown that members of the class of small RNAs called Y RNAs become necessary for replication in Xenopus only after the midblastula transition (MBT), when transcription begins and gap phases are introduced into the cell cycle. The research is published in Molecular and Cellular Biology.
Initiation of DNA replication in human cells requires the function of a class of non-coding RNAs called Y RNAs. These are structured stem-loop RNAs of 70-120 nucleotides, which have been conserved in vertebrate evolution. Humans and Xenopus laevis have four Y RNAs, whereas zebrafish have only one. Y RNAs associate with unreplicated chromatin in human cell nuclei and with several proteins that are essential for the initiation of DNA replication, including ORC and Cdt1. After initiation, they are displaced from sites of replicated chromatin. Little is known about the molecular basis of Y RNA function.
Although Y RNAs are required for DNA replication in adult cells and (as this paper shows) after the MBT in Xenopus and zebrafish embryos, Jim Smith (pictured) and Clara Collart in NIMR's Division of Systems Biology, together with Torsten Krude and Christo Christov in Cambridge, have demonstrated that they are not necessary for embryonic viability or DNA replication before the MBT. Similarly, Y RNAs are not required for replication in cytoplasmic extracts from activated Xenopus eggs, which are widely used (albeit inappropriately, according to these results) as a model system to study eukaryotic DNA replication. These data also show that Y RNAs associate with embryonic chromatin only after the MBT. This association depends on the ability of Y RNAs to interact with the recognition complex.
Click image to view at full-size
Y RNA function is only necessary for DNA replication in Xenopus after the midblastula transition. The top row shows control nuclei at stages before, during and after the MBT. Nuclei are counterstained red, and green stain indicates replication. The lower row shows nuclei lacking Y RNA function, at the same stages. Replication occurs normally before the MBT but is inhibited thereafter.
Our findings identify a mode of DNA replication, before the MBT, that is independent of Y RNAs. This should help us understand how Y RNAs function and perhaps identify novel means for regulating the cell cycle in health and disease.
Jim Smith
Original article
The mid-blastula transition defines the onset of Y RNA-dependent DNA replication in Xenopus laevis (2011)
Clara Collart, Christo P Christov, James C Smith and Torsten Krude
Molecular and Cellular Biology, epub ahead of print. Publisher abstract
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