AIRN regulates genomic imprinting of a cluster of autosomal genes in cis.
AIRN Antisense of IGF2R long noncoding RNA AIR IGF2RAS
Unspliced AIRN is transcribed from an antisense promoter located in intron 2 of the Igf2r (insulin-like growth-factor type-2 receptor) gene. A number of spliced isoforms of AIRN varies in size from 500bp to ~1.4kb. AIRN long noncoding RNA is Imprinte and is expressed only from paternal allele. Unspliced AIRN is unstable, and is localised to the nucleus. Stable spliced isoforms of AIRN are found in nucleus and cytoplasm.
AIRN Regulates genomic imprinting of a cluster of autosomal genes (Igf2r, Slc22a2 and Slc22a3) in cis, on mouse chromosome 17 .
Truncation of AIRN disrupts imprinting not only of Igf2r but also the nearby non-overlapping genes Slc22a2 and Slc22a3, leading to mice with a lower birth weight . AIRN silences Igf2r through transcription alone and not via its RNA product.
AIRN forms a "cloud" over the imprinted DNA locus, binding to chromatin.
AIRN Recruits G9a histone methyltransferase to epigenetically silence Slc22a3 . Slc22a3 and Slc22a2 are only imprinted at a specific time point in placental development. Outside of this time point the AIRN "cloud"/ AIRN chromatin binding and repressive histone modification are not found on these gene loci.
Although AIRN transcription can repress Igf2r at any time, it does so less efficiently when paternal Igf2r expression is high, as in late ESC differentiation . Continuous AIRN expression is needed to maintain Igf2r silencing, but only until the paternal Igf2r promoter is methylated.
AIRN is expressed during embryonic development, in the placenta, adult brain, lung and heart. AIRN is also expressed in glial cells of the developing brain but not in neurons, explains lack of Igf2r imprinting in these neurons. In human, IGF2R gene is predominantly nonimprinted and AIRN is typically not expressed; however, expression was identified in association with 16–40% of Wilms’ tumors. Bovine AIRN is not expressed in blastocyst-stage embryos. It is expressed in an increasing proportion of embryos around the time of maternal recognition of pregnancy and is expressed following implantation .
- Wilms’tumors .
Labs working on this lncRNA
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, 1090 Vienna, Austria.
- Department of Molecular Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, The Netherlands.
- Institute of Molecular Pathology, Vienna.
- The Netherlands Cancer Institute (H5), Amsterdam.
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- Latos, P.A., Pauler, F.M., Koerner, M.V., Senergin, H.B., Hudson, Q.J., Stocsits, R.R., Allhoff, W., Stricker, S.H., Klement, R.M., Warczok, K.E. et al. (2012) Airn transcriptional overlap, but not its lncRNA products, induces imprinted Igf2r silencing. Science, 338, 1469-1472.
- Santoro, F. and F. M. Pauler (2013). "Silencing by the imprinted Airn macro lncRNA: transcription is the answer." Cell Cycle 12(5): 711-712.
- Nagano, T., et al. (2008). "The Air noncoding RNA epigenetically silences transcription by targeting G9a to chromatin." Science 322(5908): 1717-1720.
- Santoro, F., et al. (2013). "Imprinted Igf2r silencing depends on continuous Airn lncRNA expression and is not restricted to a developmental window." Development 140(6): 1184-1195.
- Yamasaki, Y., et al. (2005). "Neuron-specific relaxation of Igf2r imprinting is associated with neuron-specific histone modifications and lack of its antisense transcript Air." Hum Mol Genet 14(17): 2511-2520.
- Yotova, I. Y., et al. (2008). "Identification of the human homolog of the imprinted mouse Air non-coding RNA." Genomics 92(6): 464-473.
- Farmer, W. T., et al. (2013). "Expression of antisense of insulin-like growth factor-2 receptor RNA non-coding (AIRN) during early gestation in cattle." Anim Reprod Sci 138(1-2): 64-73.
sequence = 100271873
>gi|100271873|ref|NR_047511.1|Homo sapiens antisense of IGF2R non-protein coding RNA (AIRN), transcript variant 1, long non-coding RNA