Nagano T, Mitchell JA, Sanz LA, Pauler FM, Ferguson-Smith AC, Feil R and Fraser P (2008)
The Air non-coding RNA epigenetically silences transcription by targeting G9a to chromatin.
Science (Science Express - Available online November 6, 2008)
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Lay description
RNA has been traditionally thought of as a ‘messenger’ molecule that is copied from the DNA strands of genes in the mammalian genome. These messenger-RNAs (mRNA) encode the genetic information necessary to make protein molecules, which are vital for life. Recent discoveries have shown that most RNA molecules produced from mammalian genomes apparently contain no such information. These large ‘non-coding’ RNAs were once thought to be ‘junk’ products of the genome, but the newly appreciated vast number of these enigmatic molecules has ignited interest in their possible functions.
In this paper we investigated the potential functions of the Air non-coding RNA, which has been implicated in controlling a group of genes that regulate growth of the developing embryo. Rather than being a ‘junk product’ we found that the Air non-coding RNA actually plays a direct role in repressing gene expression by homing in on the gene promoter (the essential part of a gene that is required to switch it on). Once attached to the promoter of the gene, Air attracts specific enzymatic protein molecules and targets them to the promoter. These enzymes modify the chemical nature of the promoter, which switches the gene off.
These results provide a new understanding, showing that Air and potentially many other non-coding RNAs can play important roles in controlling genes. This work opens the door to a potentially vast, previously unappreciated regulatory network of non-coding RNA molecules that play important roles in regulating gene expression. As such, non-coding RNAs will undoubtedly be key players in normal healthy development and in instances of disease where gene control has gone wrong, such as in cancer.
About the lead author
Takashi Nagano started his professional career as an orthopaedic surgeon after graduating from Osaka University Medical School, in Japan. During his PhD course his interest in basic research inspired him to switch jobs. After completing his PhD in orthopaedic surgery, he engaged in research in developmental neuroscience and education in human histology and neuroanatomy teaching medical students, initially as a research associate and later as an assistant professor and associate professor in Niigata University and University of Fukui, in Japan. In 2004, he got a sabbatical leave and joined Peter Fraser's laboratory at the Babraham Institute as a visiting scientist and started his new research project on the Air non-coding RNA. Since 2006, he has been contracted as a Senior Research Scientist at the Babraham Institute and is keen to pursue his research career in non-coding RNA and epigenetics for the future.
This work was supported by BBSRC grant to Peter Fraser with Takashi Nagano as a named researcher. Peter Fraser is a Senior Fellow of the Medical Research Council, UK. Further information about this research can be found on the Fraser group webpages.