Premature polyadenylation of MAGI3 is associated with diminished N[superscript 6]-methyladenosine in its large internal exon
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...
| Main Authors: | , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Nature Publishing Group
2018
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| Online Access: | http://hdl.handle.net/1721.1/119787 https://orcid.org/0000-0003-1533-6730 https://orcid.org/0000-0002-9703-1780 |
| Summary: | 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. |
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