MEG3 explained

MEG3 (maternally expressed 3) is a maternally expressed, imprinted long non-coding RNA gene.^[1] At least 12 different isoforms of MEG3 are generated by alternative splicing.^[2] Expression of MEG3 is lost in cancer cells.^[3] It acts as a growth suppressor in tumour cells, and activates p53.^[4] 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.^[5] MEG3 is thought to play a role in the development of Alzheimer's disease by triggering necroptosis.^{[6] [7]}

See also

• Long noncoding RNA

Further reading

• Zhao J, Zhang X, Zhou Y, Ansell PJ, Klibanski A . 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 . 2006 . 16793321 . 10.1016/j.biocel.2006.05.004 .
• Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S . 6 . Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes . Genome Research . 16 . 1 . 55–65 . January 2006 . 16344560 . 1356129 . 10.1101/gr.4039406 .
• Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA . 6 . Large-scale concatenation cDNA sequencing . Genome Research . 7 . 4 . 353–8 . April 1997 . 9110174 . 139146 . 10.1101/gr.7.4.353 .
• Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA . A "double adaptor" method for improved shotgun library construction . Analytical Biochemistry . 236 . 1 . 107–13 . April 1996 . 8619474 . 10.1006/abio.1996.0138 .

Notes and References

1. Web site: Entrez Gene: MEG3 maternally expressed 3.
2. Zhang X, Rice K, Wang Y, Chen W, Zhong Y, Nakayama Y, Zhou Y, Klibanski A . 6 . Maternally expressed gene 3 (MEG3) noncoding ribonucleic acid: isoform structure, expression, and functions . Endocrinology . 151 . 3 . 939–47 . March 2010 . 20032057 . 2840681 . 10.1210/en.2009-0657 .
3. Zhang X, Zhou Y, Mehta KR, Danila DC, Scolavino S, Johnson SR, Klibanski A . A pituitary-derived MEG3 isoform functions as a growth suppressor in tumor cells . The Journal of Clinical Endocrinology and Metabolism . 88 . 11 . 5119–26 . November 2003 . 14602737 . 10.1210/jc.2003-030222 . free .
4. Zhou Y, Zhong Y, Wang Y, Zhang X, Batista DL, Gejman R, Ansell PJ, Zhao J, Weng C, Klibanski A . 6 . Activation of p53 by MEG3 non-coding RNA . The Journal of Biological Chemistry . 282 . 34 . 24731–42 . August 2007 . 17569660 . 10.1074/jbc.M702029200 . free .
5. Miyoshi N, Wagatsuma H, Wakana S, Shiroishi T, Nomura M, Aisaka K, Kohda T, Surani MA, Kaneko-Ishino T, Ishino F . 6 . 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 . March 2000 . 10759892 . 10.1046/j.1365-2443.2000.00320.x . free .
6. 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.
7. News: 2023-09-15 . Scientists discover how brain cells die in Alzheimer's . en-GB . BBC News . 2023-09-27.