| BARTOŠOVIČ, Marek, Helena COVELO MOLARES, Pavlína GREGOROVÁ, Dominika HROŠŠOVÁ, G. KUDLA and 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, vol. 45, No 19, p. 11356-11370. ISSN 0305-1048. Available from: https://dx.doi.org/10.1093/nar/gkx778. |
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@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 and 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, vol.~45, No~19, p.~11356-11370. ISSN~0305-1048. Available from: https://dx.doi.org/10.1093/nar/gkx778.
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