Difference between revisions of "ENST00000609176.1"
| Line 13: | Line 13: | ||
===Characteristics=== | ===Characteristics=== | ||
| − | 108 kb (unspliced). Transcribed from an antisense promoter located in intron 2 of the Igf2r (insulin-like growth-factor type-2 receptor) gene | + | 108 kb (unspliced). Transcribed from an antisense promoter located in intron 2 of the Igf2r (insulin-like growth-factor type-2 receptor) gene<ref name="ref1"/><ref name="ref2"/>. |
| − | Also a number of spliced isoforms from 500bp to ~1.4kb | + | Also a number of spliced isoforms from 500bp to ~1.4kb<ref name="ref3"/>. |
| − | Imprinted, expressed only from paternal allele | + | Imprinted, expressed only from paternal allele<ref name="ref1"/><ref name="ref2"/>. |
===Function=== | ===Function=== | ||
| − | Regulates genomic imprinting of a cluster of autosomal genes (Igf2r, Slc22a2 and Slc22a3) in cis, on mouse chromosome 17 | + | Regulates genomic imprinting of a cluster of autosomal genes (Igf2r, Slc22a2 and Slc22a3) in cis, on mouse chromosome 17 <ref name="ref4"/>. |
| − | 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 | + | 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 <ref name="ref4"/>. |
| − | Air RNA forms a "cloud" over the imprinted DNA locus, binding to chromatin. Recruits G9a histone methyltransferase to epigenetically silence Slc22a3 | + | Airn silences Igf2r through transcription alone and not via its RNA product<ref name="ref12"/>. Airn may regulate imprinted expression of genes within the Igf2r/Airn cluster by accumulating at promoter sites and recruiting histone modifying enzymes to epigenetically silence transcription<ref name="ref9"/>-- |
| − | + | Air RNA forms a "cloud" over the imprinted DNA locus, binding to chromatin. Recruits G9a histone methyltransferase to epigenetically silence Slc22a3 <ref name="ref5"/>, but Igf2r is not silenced by this mechanism, | |
| − | 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 | + | Airn may induce imprinted Igf2r expression by creating an expression bias between the maternal and paternal alleles<ref name="ref9"/>. |
| + | 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<ref name="ref5"/>. | ||
===Regulation=== | ===Regulation=== | ||
Please input regulation information here. | Please input regulation information here. | ||
| + | |||
| + | |||
| + | [[File: Airn.png |right|frame| Airn can silence Igf2r at any time by transcriptional overlap [<ref name="ref12"/>]]] | ||
===Expression=== | ===Expression=== | ||
| − | |||
| − | Expressed in | + | Expressed during embryonic development, in the placenta<ref name="ref1"/><ref name="ref2"/>, adult brain, lung and heart<ref name="ref3"/>. |
| − | Unspliced Air is unstable, localised to the nucleus. Spliced isoforms, found in nucleus and cytoplasm, are more stable | + | Expressed in glial cells of the developing brain but not in neurons, explains lack of Igf2r imprinting in these neurons<ref name="ref6"/>. |
| + | |||
| + | Unspliced Air is unstable, localised to the nucleus. Spliced isoforms, found in nucleus and cytoplasm, are more stable<ref name="ref3"/>. | ||
| + | |||
| + | Airn expression is necessary to initiate paternal-specific silencing of the Igf2r gene, which is followed by gain of a somatic DNA methylation imprint on the silent Igf2r promoter<ref name="ref11"/><ref name="ref10"/>. So continuous Airn expression is needed to maintain Igf2r silencing, but only until the paternal Igf2r promoter is methylated<ref name="ref10"/>. Igf2r silencing does not require any part of the Airn lncRNA, but only transcription through the Igf2r promoter. | ||
| + | |||
| + | In the human, the IGF2R gene is predominantly nonimprinted and AIRN is typically not expressed; however, expression was identified in association with 16–40% of Wilms’ tumors<ref name="ref9"/>. Additionally, while human AIRN ncRNA is not expressed in most tissues, a competent IGF2R/AIRN imprinting cluster has been identified<ref name="ref9"/>. | ||
| + | |||
| + | In mice, loss of the maintenance DNA methylation enzyme, de novo methyltransferase 1 (Dnmt1), resulted in reduced expression of Igf2r and increased expression of Airn<ref name="ref9"/>. | ||
===Conservation=== | ===Conservation=== | ||
| − | All characterisation been carried out in mouse. Recently Air has been identified in human | + | All characterisation been carried out in mouse. Recently Air has been identified in human<ref name="ref7"/>but full length transcripts have yet to be characterised. |
===Allelic Information and Variation=== | ===Allelic Information and Variation=== | ||
Please input allelic information and variation information here. | Please input allelic information and variation information here. | ||
===Misc=== | ===Misc=== | ||
| − | Nb: Genebank and NCBI Gene sequences for Air are all for the spliced mouse isoforms. See http://www.ncbi.nlm.nih.gov/gene/104103. UCSC browser link below is for transcript variant 3 which covers a similar length to the unspliced transcript | + | Nb: Genebank and NCBI Gene sequences for Air are all for the spliced mouse isoforms. See http://www.ncbi.nlm.nih.gov/gene/104103. UCSC browser link below is for transcript variant 3 which covers a similar length to the unspliced transcript<ref name="ref8"/>. |
===Evolution=== | ===Evolution=== | ||
| Line 52: | Line 63: | ||
==Labs working on this lncRNA== | ==Labs working on this lncRNA== | ||
| − | + | ||
| + | Institute of Molecular Pathology, Vienna, Austria<ref name="ref2"/>. | ||
==References== | ==References== | ||
| − | + | <references> | |
| + | <ref name="ref1"> 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. </ref> | ||
| + | <ref name="ref2"> Wutz, A., et al. (1997). "Imprinted expression of the Igf2r gene depends on an intronic CpG island." Nature 389(6652): 745-749. </ref> | ||
| + | <ref name="ref3">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.</ref> | ||
| + | <ref name="ref4"> Sleutels, F., et al. (2002). "The non-coding Air RNA is required for silencing autosomal imprinted genes." Nature 415(6873): 810-813.</ref> | ||
| + | <ref name="ref5"> Nagano, T., et al. (2008). "The Air noncoding RNA epigenetically silences transcription by targeting G9a to chromatin." Science 322(5908): 1717-1720. </ref> | ||
| + | <ref name="ref6">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. </ref> | ||
| + | <ref name="ref7"> Yotova, I. Y., et al. (2008). "Identification of the human homolog of the imprinted mouse Air non-coding RNA." Genomics 92(6): 464-473. </ref> | ||
| + | <ref name="ref8"> Brosens, I., et al. (2013). "Defective myometrial spiral artery remodelling as a cause of major obstetrical syndromes in endometriosis and adenomyosis." Placenta 34(2): 100-105.</ref> | ||
| + | <ref name="ref9">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.</ref> | ||
| + | <ref name="ref10">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. </ref> | ||
| + | <ref name="ref11"> Kobayashi, H., et al. (2013). "Epigenetic and transcriptional features of the novel human imprinted lncRNA GPR1AS suggest it is a functional ortholog to mouse Zdbf2linc." Epigenetics 8(6): 635-645.</ref> | ||
| + | <ref name="ref12"> Santoro, F. and F. M. Pauler (2013). "Silencing by the imprinted Airn macro lncRNA: transcription is the answer." Cell Cycle 12(5): 711-712.</ref> | ||
| + | </references> | ||
| + | |||
{{basic| | {{basic| | ||
Revision as of 07:01, 15 October 2014
Please input one-sentence summary here.
Contents
Annotated Information
Transcriptomic Nomeclature
Please input transcriptomic nomeclature information here.
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].
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]. Airn may regulate imprinted expression of genes within the Igf2r/Airn cluster by accumulating at promoter sites and recruiting histone modifying enzymes to epigenetically silence transcription[6]-- Air RNA forms a "cloud" over the imprinted DNA locus, binding to chromatin. Recruits G9a histone methyltransferase to epigenetically silence Slc22a3 [7], but Igf2r is not silenced by this mechanism, Airn may induce imprinted Igf2r expression by creating an expression bias between the maternal and paternal alleles[6]. 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].
Regulation
Please input regulation information here.
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[8].
Unspliced Air is unstable, localised to the nucleus. Spliced isoforms, found in nucleus and cytoplasm, are more stable[3].
Airn expression is necessary to initiate paternal-specific silencing of the Igf2r gene, which is followed by gain of a somatic DNA methylation imprint on the silent Igf2r promoter[9][10]. So continuous Airn expression is needed to maintain Igf2r silencing, but only until the paternal Igf2r promoter is methylated[10]. Igf2r silencing does not require any part of the Airn lncRNA, but only transcription through the Igf2r promoter.
In the human, the IGF2R gene is predominantly nonimprinted and AIRN is typically not expressed; however, expression was identified in association with 16–40% of Wilms’ tumors[6]. Additionally, while human AIRN ncRNA is not expressed in most tissues, a competent IGF2R/AIRN imprinting cluster has been identified[6].
In mice, loss of the maintenance DNA methylation enzyme, de novo methyltransferase 1 (Dnmt1), resulted in reduced expression of Igf2r and increased expression of Airn[6].
Conservation
All characterisation been carried out in mouse. Recently Air has been identified in human[11]but full length transcripts have yet to be characterised.
Allelic Information and Variation
Please input allelic information and variation information here.
Misc
Nb: Genebank and NCBI Gene sequences for Air are all for the spliced mouse isoforms. See http://www.ncbi.nlm.nih.gov/gene/104103. UCSC browser link below is for transcript variant 3 which covers a similar length to the unspliced transcript[12].
Evolution
Please input evolution information here.
You can also add sub-section(s) at will.
Labs working on this lncRNA
Institute of Molecular Pathology, Vienna, Austria[2].
References
- ↑ 1.0 1.1 1.2 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 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 Santoro, F. and F. M. Pauler (2013). "Silencing by the imprinted Airn macro lncRNA: transcription is the answer." Cell Cycle 12(5): 711-712.
- ↑ 6.0 6.1 6.2 6.3 6.4 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.
- ↑ 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.
- ↑ 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.
- ↑ Kobayashi, H., et al. (2013). "Epigenetic and transcriptional features of the novel human imprinted lncRNA GPR1AS suggest it is a functional ortholog to mouse Zdbf2linc." Epigenetics 8(6): 635-645.
- ↑ 10.0 10.1 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.
- ↑ Yotova, I. Y., et al. (2008). "Identification of the human homolog of the imprinted mouse Air non-coding RNA." Genomics 92(6): 464-473.
- ↑ Brosens, I., et al. (2013). "Defective myometrial spiral artery remodelling as a cause of major obstetrical syndromes in endometriosis and adenomyosis." Placenta 34(2): 100-105.
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 |
