ENST00000609176.1

From LncRNAWiki
Revision as of 09:35, 15 October 2014 by Linxia (talk | contribs)
Jump to: navigation, search

Please input one-sentence summary here.

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]. 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].

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[8]. So continuous Airn expression is needed to maintain Igf2r silencing, but only until the paternal Igf2r promoter is methylated[8]. Igf2r silencing does not require any part of the Airn lncRNA, but only transcription through the Igf2r promoter.

Regulation

The unmethlyated ICR acts as promoter for Airn, which then silence all imprinted genes in the cluster on that parental allele[9].

Expression

Airn can silence Igf2r at any time by transcriptional overlap [[5]]

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[10].

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[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[11][6].


Conservation

All characterisation been carried out in mouse. Recently Air has been identified in human[12].


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. 8.0 8.1 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.
  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. 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.
  11. 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.
  12. Yotova, I. Y., et al. (2008). "Identification of the human homolog of the imprinted mouse Air non-coding RNA." Genomics 92(6): 464-473.


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
[back to top]