N6-methyladenosine (m6A) and N6,2'-O-dimethyladenosine (m6Am) are two abundant modifications found in mRNAs and ncRNAs that can regulate multiple aspects of RNA biology. They function mainly by regulating interactions with specific RNA-binding proteins. Both modifications are linked to development, disease and stress response. To date, three methyltransferases and two demethylases have been identified that modify adenosines in mammalian mRNAs. Here, we present a comprehensive analysis of the interactomes of these enzymes. PCIF1 protein network comprises mostly factors involved in nascent RNA synthesis by RNA polymerase II, whereas ALKBH5 is closely linked with most aspects of pre-mRNA processing and mRNA export to the cytoplasm. METTL16 resides in subcellular compartments co-inhabited by several other RNA modifiers and processing factors. FTO interactome positions this demethylase at a crossroad between RNA transcription, RNA processing and DNA replication and repair. Altogether, these enzymes share limited spatial interactomes, pointing to specific molecular mechanisms of their regulation.

• MeSH
• adaptorové proteiny signální transdukční genetika   metabolismus   MeSH
• adenosin analogy a deriváty   metabolismus   MeSH
• alfa-ketoglutarát-dependentní dioxygenasa, AlkB homolog 5 genetika   metabolismus   MeSH
• anotace sekvence MeSH
• gen pro FTO genetika   metabolismus   MeSH
• genetická transkripce MeSH
• genová ontologie MeSH
• HEK293 buňky MeSH
• jaderné proteiny genetika   metabolismus   MeSH
• lidé MeSH
• mapování interakce mezi proteiny MeSH
• messenger RNA genetika   metabolismus   MeSH
• methyltransferasy genetika   metabolismus   MeSH
• N-demethylasy genetika   metabolismus   MeSH
• nekódující RNA genetika   metabolismus   MeSH
• oprava DNA MeSH
• protein - isoformy genetika   metabolismus   MeSH
• replikace DNA MeSH
• vazba proteinů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

N6-methyladenosine (m6A) 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 m6A. Besides, deletion of intronic region that contains m6A-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 m6A. Our results reveal for the first time the dynamic connection between FTO RNA binding and demethylation activity that influences several mRNA processing events.

• MeSH
• 3' nepřekládaná oblast genetika   MeSH
• adenosin analogy a deriváty   metabolismus   MeSH
• alternativní sestřih * MeSH
• exony genetika   MeSH
• gen pro FTO genetika   metabolismus   MeSH
• HEK293 buňky MeSH
• introny genetika   MeSH
• lidé MeSH
• methyltransferasy genetika   metabolismus   MeSH
• mutace MeSH
• mutageneze cílená MeSH
• poly A genetika   MeSH
• prekurzory RNA genetika   metabolismus   MeSH
• stanovení celkové genové exprese metody   MeSH
• vazba proteinů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: To investigate the contraceptive behaviour of Czech and Romanian women and their attitudes towards different forms of contraception. STUDY DESIGN: Anonymous questionnaire research among 1011 Czech and 1001 Romanian women between 15 and 50 years of age. The samples were representative of both the Czech and Romanian female populations with respect to age, education and the size of their place of residence. RESULTS: The majority of women use contraception when in a stable sexual relationship. We found a higher percentage of women using contraception among Czech women. Romanian women more often use less reliable methods in a stable relationship, and condoms. Czech women use hormonal contraception much more. Women in the Czech Republic would more often agree to use a condom and, in particular, to use hormonal and intrauterine contraception. More Romanian women than Czech women prefer the method of infertile days. The use of contraception is influenced by the factors of age, education and size of the place of residence. CONCLUSION: The majority of Czech and Romanian women protect themselves against unwanted pregnancy. Czech women are more frequent users of contraceptives in general and, in particular, of hormonal contraception. Romanian women tend to use less reliable methods of contraception but on the other hand, they more often use condoms as a means of protection.

• MeSH
• antikoncepce metody   MeSH
• antikoncepční chování statistika a číselné údaje   MeSH
• dospělí MeSH
• kondomy využití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• těhotenství MeSH
• zdraví - znalosti, postoje, praxe MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Geografické názvy
• Česká republika MeSH
• Rumunsko MeSH