Premature polyadenylation of MAGI3 is associated with diminished N[superscript 6]-methyladenosine in its large internal exon
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Author(s)
Ni, Thomas K.
Elman, Jessica S.
Kuperwasser, Charlotte
Jin, Dexter X.
Gupta, Piyush
Date Issued
January 2018
Journal
Scientific Reports
Publisher
Nature Publishing Group
Citation
Ni, Thomas K., et al. “Premature Polyadenylation of MAGI3 Is Associated with Diminished N[superscript 6]-Methyladenosine in Its Large Internal Exon.” Scientific Reports, vol. 8, no. 1, Dec. 2018. © 2018 Springer Nature Publishing AG
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Final published version
Abstract
In cancer, tumor suppressor genes (TSGs) are frequently truncated, causing their encoded products to be non-functional or dominant-negative. We previously showed that premature polyadenylation (pPA) of MAGI3 truncates the gene, switching its functional role from a TSG to a dominant-negative oncogene. Here we report that MAGI3 undergoes pPA at the intron immediately downstream of its large internal exon, which is normally highly modified by N[superscript 6]-methyladenosine (m[superscript 6]A). In breast cancer cells that upregulate MAGI3[superscript pPA], m[superscript 6]A levels in the large internal exon of MAGI3 are significantly reduced compared to cells that do not express MAGI3[superscript pPA]. We further find that MAGI3[superscript pPA] transcripts are significantly depleted of m[superscript 6]A modifications, in contrast to highly m6A-modified full-length MAGI3 mRNA. Finally, we analyze public expression data and find that other TSGs, including LATS1 and BRCA1, also undergo intronic pPA following large internal exons, and that m[superscript 6]A levels in these exons are reduced in pPA-activated breast cancer cells relative to untransformed mammary cells. Our study suggests that m6A may play a role in regulating intronic pPA of MAGI3 and possibly other TSGs, warranting further investigation.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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DOI of Published Version
https://doi.org/10.1038/s41598-018-19916-8
