Premature polyadenylation of MAGI3 is associated with diminished N 6 -methyladenosine in its large internal exon.

Autor: Ni TK; Department of Developmental, Chemical and Molecular Biology, Tufts University School of Medicine, 136 Harrison Ave, Boston, MA, 02111, USA.; Raymond & Beverly Sackler Convergence Laboratory, Tufts University School of Medicine, 136 Harrison Ave, Boston, MA, 02111, USA.; Molecular Oncology Research Institute, Tufts Medical Center, 800 Washington St, Boston, MA, 02111, USA., Elman JS; Department of Developmental, Chemical and Molecular Biology, Tufts University School of Medicine, 136 Harrison Ave, Boston, MA, 02111, USA.; Raymond & Beverly Sackler Convergence Laboratory, Tufts University School of Medicine, 136 Harrison Ave, Boston, MA, 02111, USA.; Molecular Oncology Research Institute, Tufts Medical Center, 800 Washington St, Boston, MA, 02111, USA., Jin DX; Whitehead Institute for Biomedical Research, Cambridge, MA, 02142, USA.; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA., Gupta PB; Whitehead Institute for Biomedical Research, Cambridge, MA, 02142, USA.; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA., Kuperwasser C; Department of Developmental, Chemical and Molecular Biology, Tufts University School of Medicine, 136 Harrison Ave, Boston, MA, 02111, USA. charlotte.kuperwasser@tufts.edu.; Raymond & Beverly Sackler Convergence Laboratory, Tufts University School of Medicine, 136 Harrison Ave, Boston, MA, 02111, USA. charlotte.kuperwasser@tufts.edu.; Molecular Oncology Research Institute, Tufts Medical Center, 800 Washington St, Boston, MA, 02111, USA. charlotte.kuperwasser@tufts.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2018 Jan 23; Vol. 8 (1), pp. 1415. Date of Electronic Publication: 2018 Jan 23.
DOI: 10.1038/s41598-018-19916-8
Abstrakt: 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 6 -methyladenosine (m 6 A). In breast cancer cells that upregulate MAGI3 pPA , m 6 A levels in the large internal exon of MAGI3 are significantly reduced compared to cells that do not express MAGI3 pPA . We further find that MAGI3 pPA transcripts are significantly depleted of m 6 A modifications, in contrast to highly m 6 A-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 6 A levels in these exons are reduced in pPA-activated breast cancer cells relative to untransformed mammary cells. Our study suggests that m 6 A may play a role in regulating intronic pPA of MAGI3 and possibly other TSGs, warranting further investigation.
Databáze: MEDLINE
Externí odkaz: