NONHSAT017465

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Annotated Information

Name

H19

Characteristics

2.3 kb. Imprinted at the Igf2 locus (Bartolomei (1991), Zemel (1992)).

Also contains a microRNA (miR-675) in exon one (Cai (2007)).

Function

Complex functions:
Influences growth via control of Igf2 expression, with a H19 knockout showing an overgrowth phenotype due in part to bi-allelic expression of Igf2 (Ripoche (1997)).
Can also function in trans to downregulate the expression of a number of imprinted genes in the hypothesised Imprinted Gene Network (IGN) including Igf2r, Dlk1 etc. Allowing H19 to regulate growth during development (Gabory (2009)).
Implicated as both a tumor suppressor (Hao (1993), Yoshimizu (2008)) and an oncogene upregulated by c-myc and hypoxia (Matouk (2007), Barsyte-Lovejoy (2006) and references therein). A number of reports have also shown upregulation / reactivation of H19 in various cancers although the functional significance (if any) is unclear in many cases (Gabory (2010), Adriaenssens (1998)).
The mode of action by which H19 functions is still unclear: . Focusing on its regulation of Igf2, H19 has been hypothesised to act at the level of transcription since an H19 knockout lead to methylation changes and loss of imprinting of Igf2 (Ripoche (1997), Forn®¶ (1997)). However, H19 can bind Igf2 mRNA binding-protein (IMP) family members (Runge (2000)), which appear to act to promote translation of Igf2 (Hansen (2004), Liao (2005)), therefore competition between Igf2 and H19 for IMP1 binding may allow H19 to regulate Igf2 post-transcriptionally.
Both sense and antisense transcripts from the H19 locus were identified as binding to the PRC2 chromatin modification complex in mouse embryonic stem cells, suggesting a potential function for H19 RNA (Zhao (2010)).
miR-675 may be responsible for the oncogenic activity of H19 as it was found to down-regulate the tumour suppressor retinoblastoma (RB) in human colorectal cancer, causing increased tumour cell growth (Tsang (2010)). Also, in adult human chondrocytes, expression of H19 (and subsequently miR-675) is driven by SOX9 with miR-675 acting to positively regulate COL2A1 which encodes a collagen protein important to the cartilage matrix (Dudek (2010)).
H19 appears to be a bi-functional RNA acting as both a miRNA and a lncRNA. Such properties may help to explain the conflicting reports that it is both a tumour suppressor and an oncogene (Smits (2008)). Additionally its effect on tumour development may be heavily context dependent (Gabory (2010)).

Expression

Expressed from the maternal allele, while the neighbouring Igf2 gene is transcribed from the paternal allele (Bartolomei (1991)).

In mice, H19 is activated in extra-embryonic cell types at the time of implantation. Strongly expressed during embryogenesis, down-regulated after birth with strong expression only retained in skeletal muscle and cartilage (Pachnis (1984), Pachnis (1988), Poirier (1991), Castle (2010), Dudek (2010)); upregulated in various tumors (Matouk (2007)).
Can be found in both the nucleus and the cytoplasm (Runge (2000), Schoenfelder (2007), Brannan (1990)).

Conservation

Conserved and imprinted in therians (eutherians and marsupials). Both the miRNA and the H19 lncRNA exon structure are conserved (Smits (2008)).

Misc

First long noncoding RNA described in mammalian cells (Brannan (1990)). Gabory 2010 provides a useful review of some of the extensive literature on H19 (Gabory (2010)).

Transcriptomic Nomeclature

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Regulation

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Allelic Information and Variation

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Evolution

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Labs working on this lncRNA

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References

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Basic Information

Transcript ID	NONHSAT017465
Source	NONCODE4.0
Same with	,
Classification	intergenic
Length	2322 nt
Genomic location	chr11-:2016406..2019105
Exon number	5
Exons	2016406..2017024,2017106..2017228,2017309..2017421,2017517..2017651,2017748..2019105
Genome context
Sequence	000001 GGGAGGGGGT GGGATGGGTG GGGGGTAACG GGGGAAACTG GGGAAGTGGG GAACCGAGGG GCAACCAGGG GAAGATGGGG 000080 000081 TGCTGGAGGA GAGCTTGTGG GAGCCAAGGA GCACCTTGGA CATCTGGAGT CTGGCAGGAG TGATGACGGG TGGAGGGGCT 000160 000161 AGCTCGAGGC AGGGCTGGTG GGGCCTGAGG CCAGTGAGGA GTGTGGAGTA GGCGCCCAGG CATCGTGCAG ACAGGGCGAC 000240 000241 ATCAGCTGGG GACGATGGGC CTGAGCTAGG GCTGGAAAGA AGGGGGAGCC AGGCATTCAT CCCGGTCACT TTTGGTTACA 000320 000321 GGACGTGGCA GCTGGTTGGA CGAGGGGAGC TGGTGGGCAG GGTTTGATCC CAGGGCCTGG GCAACGGAGG TGTAGCTGGC 000400 000401 AGCAGCGGGC AGGTGAGGAC CCCATCTGCC GGGCAGGTGA GTCCCTTCCC TCCCCAGGCC TCGCTTCCCC AGCCTTCTGA 000480 000481 AAGAAGGAGG TTTAGGGGAT CGAGGGCTGG CGGGGAGAAG CAGACACCCT CCCAGCAGAG GGGCAGGATG GGGGCAGGAG 000560 000561 AGTTAGCAAA GGTGACATCT TCTCGGGGGG AGCCGAGACT GCGCAAGGCT GGGGGGTTAT GGGCCCGTTC CAGGCAGAAA 000640 000641 GAGCAAGAGG GCAGGGAGGG AGCACAGGGG TGGCCAGCGT AGGGTCCAGC ACGTGGGGTG GTACCCCAGG CCTGGGTCAG 000720 000721 ACAGGGACAT GGCAGGGGAC ACAGGACAGA GGGGTCCCCA GCTGCCACCT CACCCACCGC AATTCATTTA GTAGCAGGCA 000800 000801 CAGGGGCAGC TCCGGCACGG CTTTCTCAGG CCTATGCCGG AGCCTCGAGG GCTGGAGAGC GGGAAGACAG GCAGTGCTCG 000880 000881 GGGAGTTGCA GCAGGACGTC ACCAGGAGGG CGAAGCGGCC ACGGGAGGGG GGCCCCGGGA CATTGCGCAG CAAGGAGGCT 000960 000961 GCAGGGGCTC GGCCTGCGGG CGCCGGTCCC ACGAGGCACT GCGGCCCAGG GTCTGGTGCG GAGAGGGCCC ACAGTGGACT 001040 001041 TGGTGACGCT GTATGCCCTC ACCGCTCAGC CCCTGGGGCT GGCTTGGCAG ACAGTACAGC ATCCAGGGGA GTCAAGGGCA 001120 001121 TGGGGCGAGA CCAGACTAGG CGAGGCGGGC GGGGCGGAGT GAATGAGCTC TCAGGAGGGA GGATGGTGCA GGCAGGGGTG 001200 001201 AGGAGCGCAG CGGGCGGCGA GCGGGAGGCA CTGGCCTCCA GAGCCCGTGG CCAAGGCGGG CCTCGCGGGC GGCGACGGAG 001280 001281 CCGGGATCGG TGCCTCAGCG TTCGGGCTGG AGACGAGGCC AGGTCTCCAG CTGGGGTGGA CGTGCCCACC AGCTGCCGAA 001360 001361 GGCCAAGACG CCAGGTCCGG TGGACGTGAC AAGC