Maternally Expressed Gene 3 (MEG3) Noncoding Ribonucleic Acid: Isoform Structure, Expression, and Functions
Open accessAbstract
Maternally expressed gene 3 (MEG3) is an imprinted gene highly expressed in the human pituitary. However, MEG3 expression is lost in human gonadotroph-derived pituitary adenomas and most human tumor cell lines. Expression of MEG3 in tumor cells results in growth suppression, p53 protein increase, and activation of p53 downstream targets. The MEG3 gene encodes a noncoding RNA of approximately 1700 nucleotides. There are 12 different MEG3 gene transcripts, generated by alternative splicing. They contain the common exons 1-3 and exons 8-10, but each uses one or more exons 4-7 in a different combination in the middle. MEG3 isoform expression patterns are tissue and cell type specific. Functionally, each isoform stimulates p53-mediated transactivation and suppresses tumor cell growth. We analyzed the secondary RNA folding structure of each MEG3 isoform, using the computer program mfold. All MEG3 RNA isoforms contain three distinct secondary folding motifs M1, M2, and M3. Deletion analysis showed that motifs M2 and M3 are important for p53 activation. Furthermore, a hybrid MEG3 RNA, containing a piece of artificially synthesized sequence different from the wild type but folding into a similar secondary structure, retained the functions of both p53 activation and growth suppression. These results support the hypothesis that a proper folding structure of the MEG3 RNA molecule is critical for its biological functions. This study establishes for the first time the structure-function relationship of a large noncoding RNA and provides a first look into the molecular mechanisms of the biological functions of a large noncoding RNA.
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MEG3 is an imprinted gene located on chromosome 14q32.3 in humans and functions as a lncRNA.
“Maternally expressed gene 3 (MEG3), also known as gene trap locus 2 (Gtl2), is an imprinted gene located on chromosome 14q32.3 in humans and functions as a lncRNA19.”
From Long non-coding RNA MEG3 functions as a competing endogenous RNA to regulate ischemic neuronal death by targeting miR-21/PDCD4 signaling pathway (2017) · cites this paper as [19]
The Abstract identifies human MEG3 as an imprinted gene that encodes a noncoding RNA, supporting its description as a lncRNA. Our copy does not state that MEG3 is located at human chromosome 14q32.3; a reference title mentions a 14q32.2 imprinted region but does not establish the claimed location. (LLM, conf=0.86)
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- Authors
- Zhang, X., Rice, K., Wang, Y., Chen, W., Zhong, Y., Nakayama, Y., Zhou, Y., & Klibanski, A.
- Affiliations
- Harvard University (US)
- Corresponding author
- Klibanski, Anne
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2009-12-23
- Volume
- 151
- Issue
- 3
- Pages
- 939-947
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- PMC
- PMC2840681
- OpenAlex
- W2066815559
- Cited by
- 325
- References
- 19
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 17 · 2023: 25 · 2022: 16 · 2021: 23 · 2020: 35 · 2019: 21 · 2018: 29 · 2017: 30 · 2016: 17 · 2015: 28 · 2014: 21 · 2013: 18 · 2012: 17
- FWCI
- 3.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Endocrinology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK040947, R01-DK-40947)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- MEG3, imprinted genes, non-coding RNA, RNA isoforms, alternative splicing, p53 activation, structure-function relationship, pituitary adenoma, tumor growth inhibition
- MeSH terms
- Base Sequence, Cell Line, Humans, Molecular Sequence Data, Nucleic Acid Conformation, Pituitary Neoplasms, Proteins, Structure-Activity Relationship, Gene Expression, Tumor Suppressor Protein p53, DNA, Complementary, RNA, Untranslated, RNA, Long Noncoding
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