BARTOŠOVIČ, Marek, Helena COVELO MOLARES, Pavlína GREGOROVÁ, Dominika HROŠŠOVÁ, G. KUDLA a Štěpánka VAŇÁČOVÁ. N6-methyladenosine demethylase FTO targets pre-mRNAs and regulates alternative splicing and 3'-end processing. Nucleic Acids Research. Oxford: Oxford University Press, 2017, roč. 45, č. 19, s. 11356-11370. ISSN 0305-1048. Dostupné z: https://dx.doi.org/10.1093/nar/gkx778. |
Další formáty:
BibTeX
LaTeX
RIS
@article{1409373, author = {Bartošovič, Marek and Covelo Molares, Helena and Gregorová, Pavlína and Hroššová, Dominika and Kudla, G. and Vaňáčová, Štěpánka}, article_location = {Oxford}, article_number = {19}, doi = {http://dx.doi.org/10.1093/nar/gkx778}, keywords = {EMBRYONIC STEM-CELLS; BLOCKED 5' TERMINI; SEX DETERMINATION; COMPREHENSIVE ANALYSIS; NUCLEAR-RNA; METHYLATION; DROSOPHILA; REVEALS; OBESITY; N-6-METHYLADENOSINE}, language = {eng}, issn = {0305-1048}, journal = {Nucleic Acids Research}, title = {N6-methyladenosine demethylase FTO targets pre-mRNAs and regulates alternative splicing and 3'-end processing}, url = {https://academic.oup.com/nar/article/45/19/11356/4097621}, volume = {45}, year = {2017} }
TY - JOUR ID - 1409373 AU - Bartošovič, Marek - Covelo Molares, Helena - Gregorová, Pavlína - Hroššová, Dominika - Kudla, G. - Vaňáčová, Štěpánka PY - 2017 TI - N6-methyladenosine demethylase FTO targets pre-mRNAs and regulates alternative splicing and 3'-end processing JF - Nucleic Acids Research VL - 45 IS - 19 SP - 11356-11370 EP - 11356-11370 PB - Oxford University Press SN - 03051048 KW - EMBRYONIC STEM-CELLS KW - BLOCKED 5' TERMINI KW - SEX DETERMINATION KW - COMPREHENSIVE ANALYSIS KW - NUCLEAR-RNA KW - METHYLATION KW - DROSOPHILA KW - REVEALS KW - OBESITY KW - N-6-METHYLADENOSINE UR - https://academic.oup.com/nar/article/45/19/11356/4097621 L2 - https://academic.oup.com/nar/article/45/19/11356/4097621 N2 - N6-methyladenosine (m(6)A) is the most abundant base modification found in messenger RNAs (mRNAs). The discovery of FTO as the first m6A mRNA demethylase established the concept of reversible RNA modification. Here, we present a comprehensive transcriptome-wide analysis of RNA demethylation and uncover FTO as a potent regulator of nuclear mRNA processing events such as alternative splicing and 3' end mRNA processing. We show that FTO binds preferentially to pre-mRNAs in intronic regions, in the proximity of alternatively spliced (AS) exons and poly(A) sites. FTO knockout (KO) results in substantial changes in pre-mRNA splicing with prevalence of exon skipping events. The alternative splicing effects of FTO KO anti-correlate with METTL3 knockdown suggesting the involvement of m(6)A. Besides, deletion of intronic region that contains m(6)A-linked DRACH motifs partially rescues the FTO KO phenotype in a reporter system. All together, we demonstrate that the splicing effects of FTO are dependent on the catalytic activity in vivo and are mediated by m(6)A. Our results reveal for the first time the dynamic connection between FTO RNA binding and demethylation activity that influences several mRNA processing events. ER -
BARTOŠOVIČ, Marek, Helena COVELO MOLARES, Pavlína GREGOROVÁ, Dominika HROŠŠOVÁ, G. KUDLA a Štěpánka VAŇÁČOVÁ. N6-methyladenosine demethylase FTO targets pre-mRNAs and regulates alternative splicing and 3'-end processing. \textit{Nucleic Acids Research}. Oxford: Oxford University Press, 2017, roč.~45, č.~19, s.~11356-11370. ISSN~0305-1048. Dostupné z: https://dx.doi.org/10.1093/nar/gkx778.
|