ENST00000609176.1
Air regulates genomic imprinting of a cluster of autosomal genes in cis.
Contents
Annotated Information
Name
AIRN: Antisense of IGF2R non-protein coding RNA
AIR
IGF2RAS
Characteristics
108 kb (unspliced). Transcribed from an antisense promoter located in intron 2 of the Igf2r (insulin-like growth-factor type-2 receptor) gene[1][2].
Also a number of spliced isoforms from 500bp to ~1.4kb[3].
Imprinted, expressed only from paternal allele[1][2].
Unspliced Air is unstable, localised to the nucleus. Spliced isoforms, found in nucleus and cytoplasm, are more stable[3].
Function
Regulates genomic imprinting of a cluster of autosomal genes (Igf2r, Slc22a2 and Slc22a3) in cis, on mouse chromosome 17 [4].
Truncation of Air disrupts imprinting not only of Igf2r but also the nearby non-overlapping genes Slc22a2 and Slc22a3, leading to mice with a lower birth weight [4].
Airn silences Igf2r through transcription alone and not via its RNA product[5][6].
Air RNA forms a "cloud" over the imprinted DNA locus, binding to chromatin. Recruits G9a histone methyltransferase to epigenetically silence Slc22a3 [7].
Nb: Slc22a3 and Slc22a2 are only imprinted at a specific time point in placental development. Outside of this time point the Air "cloud"/ Air chromatin binding and repressive histone modification are not found on these gene loci[7].
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 [8]. Continuous Airn expression is needed to maintain Igf2r silencing, but only until the paternal Igf2r promoter is methylated[8].
Regulation
The unmethlyated imprint control region (ICR) acts as promoter for Airn, which then silence all imprinted genes in the cluster on that parental allele[4][5].
Expression
Expressed during embryonic development, in the placenta[1][2], adult brain, lung and heart[3].
Expressed in glial cells of the developing brain but not in neurons, explains lack of Igf2r imprinting in these neurons[9].
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[10].
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 [11].
Conservation
All characterisation been carried out in mouse. Recently Air has been identified in human[10].
Disease
alcoholic liver disease,chronic nonalcoholic liver disease, hepatocelluar carcinoma
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Labs working on this lncRNA
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, 1090 Vienna, Austria [10][5][6][8].
Department of Molecular Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, The Netherlands [4].
Institute of Molecular Pathology, Vienna, Austria[2].
The Netherlands Cancer Institute (H5), Amsterdam, The Netherlands[1].
References
Annotation originally sourced from lncRNAdb.
- ↑ 1.0 1.1 1.2 1.3 Lyle, R., et al. (2000). "The imprinted antisense RNA at the Igf2r locus overlaps but does not imprint Mas1." Nat Genet 25(1): 19-21.
- ↑ 2.0 2.1 2.2 2.3 Wutz, A., et al. (1997). "Imprinted expression of the Igf2r gene depends on an intronic CpG island." Nature 389(6652): 745-749.
- ↑ 3.0 3.1 3.2 Seidl, C. I., et al. (2006). "The imprinted Air ncRNA is an atypical RNAPII transcript that evades splicing and escapes nuclear export." EMBO J 25(15): 3565-3575.
- ↑ 4.0 4.1 4.2 4.3 Sleutels, F., et al. (2002). "The non-coding Air RNA is required for silencing autosomal imprinted genes." Nature 415(6873): 810-813.
- ↑ 5.0 5.1 5.2 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.
- ↑ 6.0 6.1 6.2 Santoro, F. and F. M. Pauler (2013). "Silencing by the imprinted Airn macro lncRNA: transcription is the answer." Cell Cycle 12(5): 711-712.
- ↑ 7.0 7.1 Nagano, T., et al. (2008). "The Air noncoding RNA epigenetically silences transcription by targeting G9a to chromatin." Science 322(5908): 1717-1720.
- ↑ 8.0 8.1 8.2 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.
- ↑ 10.0 10.1 10.2 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.
Basic Information
| Transcript ID |
ENST00000609176.1 |
| Source |
Gencode19 |
| Same with |
NONHSAT115887 |
| Classification |
intronic(AS) |
| Length |
1489 nt |
| Genomic location |
chr6-:160424323..160428696 |
| Exon number |
3 |
| Exons |
160424323..160424419,160425983..160426190,160427513..160428696 |
| Genome context |
|
| Sequence |
000001 GAAAGCACAC ACCATGCTGG AAAGGAGAGA GAAGGAAAAA CCCACTCCTA GCCACACAAT GGTGGATCTT AATATCCAAT 000080
000081 GAAAAGAAAA AATTCTAATC TAGGTCACAC ACAATAACCC AATATAAAAT GAACAAGACA TGATCAAGCA AATCAAAGAA 000160 000161 AAATGTACAT CAATAAATAT GTTAAGACAT GTTCAATGTT ACTGGTGATC AAGGAATTTC AAATCAAGAC CAAAATGGTA 000240 000241 TACCATTTAC AACCATCCCT CTGGCAAAAA TTAAATACCA AGTGTCAGCC ATGAGGTGGC TCAGAGCTCT CCTGTATTGC 000320 000321 TAGTGAAATG TTAACTGGTT CAACAACTAT GTAAGTCAGC AGGACATTAT GTCCTAAAAT TGAACATTCG TGTGCCCTAT 000400 000401 GACCTAGTTA CTCCACTCAG GTCTATATAA AAGAGAAAAC CATGCACATA TGGAACATGC ACAGCAGAAA ATGTGAAAGA 000480 000481 ATATCTCATG CTCTTCAGAA GAGCAAAAAC CTGGAAATGA CCAAAGGCCC ATCAACAGAA GAGTGGATAA ATTAACTTCA 000560 000561 GCAGATCCAC ACAAAATATC ACAGCAGTCA GAAGGAATAA ACCACAGTGA AAAACAACAA TACGGTTGAT TTTTAGTAAT 000640 000641 ATTACTGTTA TCACTTAAGT CCCAAAAAGT TACACATAGG AAGATAACTT AGTTGCAAAC ACACAGATTT TTTTTTTTTG 000720 000721 GAAATTAGAT ACAGTAAAAA AAAAAAAAAA TTAATACAAG ATGGGAGCTA ATGATTACTC CTAGCGAAAA GTGAAAGAGG 000800 000801 AAAGAGTAAA ACAGATAGTG GTTACTGCCA AGATCCTAGA TTTTTGTTGG AAACAGTGCT CGCTACATTA TACAAAACAA 000880 000881 CTAATTTTTT AAAAGGAAAA AGGTTAGTCT ATGGATTAAC ACATGGCTCA CTGTACGTGC CATGAGCTCG GGATGATAGC 000960 000961 TGATCCAATC CCATATACAC CTGAAGTCTT GGGGCAGGGG CGGACCACGA GTCAGCGCGC CCCCACAGCA CCAGGCTGAT 001040 001041 GGCCCCGTGG TTCTTCTGCC TGCAAGCAAA AGTCAGCCAC GATCATCCTT CTCCATCTGC AACACCCAGG GTCTTTTCTA 001120 001121 AAACTTTTGC CCAGTCGGCT CAGCCAAAAG GACACAGAAG CCCTGCAGAG GCTCTGAAAC CAAGCTGCCA TGGCTCCCAG 001200 001201 TTCGACATCA TGTCACCGGA GCCTGCACAG ATGAACCAAG CTTGCAACAC GGGAGGAACC TAAGCGCTGG ACTGAGGAGC 001280 001281 GGGACTGAAA TAAGAAGCGC ACACCACATG GCAAGATCCA GGATCCAATC AGATAGAGCC CTGGTGTCAT CTAATTGCAA 001360 001361 GATCCAATCA GAACACACCT CATTACCTTA TGGTATTGCC AGACTATCAG GAGAGACCAT AAATCAGATA AAAACATGAG 001440 001441 TTGTATCCAA AACTCAACCA GGTATCATCT TAAATATCCA ACAGAATTC |
