Premature polyadenylation of MAGI3 is associated with diminished N[superscript 6]-methyladenosine in its large internal exon
Author(s)
Ni, Thomas K.; Elman, Jessica S.; Kuperwasser, Charlotte; Jin, Dexter X.; Gupta, Piyush
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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.
Date issued
2018-01Department
Massachusetts Institute of Technology. Department of BiologyJournal
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
Version: Final published version
ISSN
2045-2322