MEG3

MEG3 (maternally expressed 3) is a maternally expressed, imprinted long non-coding RNA gene.^[3] At least 12 different isoforms of MEG3 are generated by alternative splicing.^[4] Expression of MEG3 is lost in cancer cells.^[4][5] It acts as a growth suppressor in tumour cells, and activates p53.^[5][6] A conserved pseudoknot in exon 3 was shown to be essential for p53 pathway upregulation. ^[7] A pituitary transcript variant has been associated with inhibited cell proliferation. Studies in mouse and sheep suggest that an upstream intergenic differentially methylated region (IG-DMR) regulates imprinting of the region. The expression profile in mouse of the co-regulated Meg3 and Dlk1 genes suggests a causative role in the pathologies found in uniparental disomy animals, characterized by defects in skeletal muscle maturation, bone formation, placenta size and organization and prenatal lethality. The sheep homolog is associated with the callipyge mutation which in heterozygous individuals affects a muscle-specific long-range control element located in the DLK1-GTL2 intergenic region and results in the callipyge muscular hypertrophy. The non-Mendelian inheritance pattern, known as polar overdominance, likely results from the combination of the cis-effect on the expression levels of genes in the DLK1-GTL2 imprinted domain, and trans interaction between the products of reciprocally imprinted genes.^[8] MEG3 is thought to play a role in the development of Alzheimer's disease by triggering necroptosis.^[9][10]

MEG3
Identifiers
Aliases	MEG3, FP504, GTL2, LINC00023, NCRNA00023, PRO0518, PRO2160, prebp1, onco-lncRNA-83, maternally expressed 3 (non-protein coding), maternally expressed 3
External IDs	OMIM: 605636; GeneCards: MEG3; OMA:MEG3 - orthologs
Gene location (Human) Chr. Chromosome 14 (human)[1] Band 14q32.2 Start 100,779,410 bp[1] End 100,861,031 bp[1]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right hemisphere of cerebellum anterior pituitary right adrenal gland adrenal cortex left adrenal cortex right adrenal cortex right frontal lobe primary visual cortex nucleus accumbens left ovary n/a More reference expression data BioGPS n/a
Orthologs Species Human Mouse Entrez 55384 n/a Ensembl ENSG00000214548 n/a UniProt n a n/a RefSeq (mRNA) NM_018514 n/a RefSeq (protein) n/a n/a Location (UCSC) Chr 14: 100.78 – 100.86 Mb n/a PubMed search [2] n/a
Wikidata
View/Edit Human

See also

• Long noncoding RNA

References

1. GRCh38: Ensembl release 89: ENSG00000214548 – Ensembl, May 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. "Entrez Gene: MEG3 maternally expressed 3".
4. Zhang X, Rice K, Wang Y, Chen W, Zhong Y, Nakayama Y, et al. (March 2010). "Maternally expressed gene 3 (MEG3) noncoding ribonucleic acid: isoform structure, expression, and functions". Endocrinology. 151 (3): 939–47. doi:10.1210/en.2009-0657. PMC 2840681. PMID 20032057.
5. Zhang X, Zhou Y, Mehta KR, Danila DC, Scolavino S, Johnson SR, Klibanski A (November 2003). "A pituitary-derived MEG3 isoform functions as a growth suppressor in tumor cells". The Journal of Clinical Endocrinology and Metabolism. 88 (11): 5119–26. doi:10.1210/jc.2003-030222. PMID 14602737.
6. Zhou Y, Zhong Y, Wang Y, Zhang X, Batista DL, Gejman R, et al. (August 2007). "Activation of p53 by MEG3 non-coding RNA". The Journal of Biological Chemistry. 282 (34): 24731–42. doi:10.1074/jbc.M702029200. PMID 17569660.
7. Uroda, Tina; Anastasakou, Eleni; Rossi, Annalisa; Teulon, Jean-Marie; Pellequer, Jean-Luc; Annibale, Paolo; Pessey, Ombeline; Inga, Alberto; Chillón, Isabel; Marcia, Marco (September 2019). "Conserved Pseudoknots in lncRNA MEG3 Are Essential for Stimulation of the p53 Pathway". Molecular Cell. 75 (5): 982–995.e9. doi:10.1016/j.molcel.2019.07.025. ISSN 1097-2765. PMC 6739425. PMID 31444106.
8. Miyoshi N, Wagatsuma H, Wakana S, Shiroishi T, Nomura M, Aisaka K, et al. (March 2000). "Identification of an imprinted gene, Meg3/Gtl2 and its human homologue MEG3, first mapped on mouse distal chromosome 12 and human chromosome 14q". Genes to Cells. 5 (3): 211–20. doi:10.1046/j.1365-2443.2000.00320.x. PMID 10759892.
9. Balusu S, Horré K, Thrupp N, Craessaerts K, Snellinx A, Serneels L, T'Syen D, Chrysidou I, Arranz AM, Sierksma A, Simrén J, Karikari TK, Zetterberg H, Chen WT, Thal DR, Salta E, Fiers M, De Strooper B. MEG3 activates necroptosis in human neuron xenografts modeling Alzheimer's disease. Science. 2023 Sep 15;381(6663):1176-1182. doi:10.1126/science.abp9556 PMID 37708272
10. "Scientists discover how brain cells die in Alzheimer's". BBC News. 2023-09-15. Retrieved 2023-09-27.

Further reading

• Zhao J, Zhang X, Zhou Y, Ansell PJ, Klibanski A (2006). "Cyclic AMP stimulates MEG3 gene expression in cells through a cAMP-response element (CRE) in the MEG3 proximal promoter region". The International Journal of Biochemistry & Cell Biology. 38 (10): 1808–20. doi:10.1016/j.biocel.2006.05.004. PMID 16793321.
• Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, et al. (January 2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Research. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
• Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, et al. (April 1997). "Large-scale concatenation cDNA sequencing". Genome Research. 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174.
• Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (April 1996). "A "double adaptor" method for improved shotgun library construction". Analytical Biochemistry. 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID 8619474.