Difference between revisions of "ENST00000609176.1"

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===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 ([http://www.ncbi.nlm.nih.gov/pubmed/10802648 (Lyle 2000)], [http://www.ncbi.nlm.nih.gov/pubmed/9338788 (Wutz 1997)]).  
+
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 ([http://www.ncbi.nlm.nih.gov/pubmed/16874305 (Seidl 2006)]).
+
Also a number of spliced isoforms from 500bp to ~1.4kb<ref name="ref3"/>.
  
Imprinted, expressed only from paternal allele ([http://www.ncbi.nlm.nih.gov/pubmed/9338788 (Wutz 1997)], [http://www.ncbi.nlm.nih.gov/pubmed/10802648 (Lyle 2000)]).
+
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 ([http://www.ncbi.nlm.nih.gov/pubmed/11845212 (Sleutels 2002)]).  
+
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 ([http://www.ncbi.nlm.nih.gov/pubmed/11845212 (Sleutels 2002)]).
+
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 ([http://www.ncbi.nlm.nih.gov/pubmed/18988810 (Nagano 2008)]). Igf2r is not silenced by this mechanism.
+
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 ([http://www.ncbi.nlm.nih.gov/pubmed/18988810 (Nagano 2008)]).
+
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 during embryonic development, in the placenta ([http://www.ncbi.nlm.nih.gov/pubmed/9338788 (Wutz 1997)], [http://www.ncbi.nlm.nih.gov/pubmed/10802648 (Lyle 2000)]), adult brain, lung and heart ([http://www.ncbi.nlm.nih.gov/pubmed/16874305 (Seidl 2006)]).
 
  
Expressed in glial cells of the developing brain but not in neurons, explains lack of Igf2r imprinting in these neurons. ([http://www.ncbi.nlm.nih.gov/pubmed/16037066 (Yamasaki 2005)])
+
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 ([http://www.ncbi.nlm.nih.gov/pubmed/16874305 (Seidl 2006)]).
+
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 ([http://www.ncbi.nlm.nih.gov/pubmed/18789384 (Yotova 2008)]) but full length transcripts have yet to be characterised.
+
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. [http://www.ncbi.nlm.nih.gov/pubmed/23232321 (Brosens 2012)]
+
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==
Please input related labs here.
+
 
 +
Institute of Molecular Pathology, Vienna, Austria<ref name="ref2"/>.
  
 
==References==
 
==References==
Please input cited references here.
+
<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.

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.


Airn can silence Igf2r at any time by transcriptional overlap [[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[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. 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. 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. 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. 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. 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. 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. 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. 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.
  9. 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. 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.
  11. Yotova, I. Y., et al. (2008). "Identification of the human homolog of the imprinted mouse Air non-coding RNA." Genomics 92(6): 464-473.
  12. 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
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