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Gene expression regulation by upstream open reading frames and human disease

Barbosa, Cristina; Peixeiro, Isabel; Romão, Luísa

Upstream open reading frames (uORFs) are major gene expression regulatory elements. In many eukaryotic mRNAs, one or more uORFs precede the initiation codon of the main coding region. Indeed, several studies have revealed that almost half of human transcripts present uORFs. Very interesting examples have shown that these uORFs can impact gene expression of the downstream main ORF by triggering mRNA decay or by ...


Nonsense-mediated decay resistance of AUG-proximal nonsense-mutated transcripts...

Peixeiro, Isabel; Barbosa, Cristina; Romão, Luísa

Apresentação oral por convite. ; Nonsense-mediated mRNA decay (NMD) is a surveillance pathway that recognizes and rapidly degrades mRNAs containing a premature termination codon (PTC). The unified model for NMD proposes that the decision of NMD triggering is the outcome of the competition between the cytoplasmatic poly(A)-binding protein 1 (PABPC1) and the NMD effector UPF1 for the termination complex. Consequ...


Control of human beta-globin mRNA stability and its impact on beta-thalassemia ...

Peixeiro, Isabel; Silva, Ana Luísa; Romão, Luísa

Messenger RNA (mRNA) stability is a critical determinant that affects gene expression. Many pathways have evolved to modulate mRNA stability in response to developmental, physiological and/or environmental stimuli. Eukaryotic mRNAs have a considerable range of half-lives, from as short as a few minutes to as long as several days. Human globin mRNAs constitute an example of highly stable mRNAs. However, a wide v...


Interaction of PABPC1 with the translation initiation complex is critical to th...

Peixeiro, Isabel; Inácio, Ângela; Barbosa, Cristina; Silva, Ana Luísa; Liebhaber, Stephen; Romão, Luísa

Nonsense-mediated mRNA decay (NMD) is a surveillance pathway that recognizes and rapidly degrades mRNAs containing premature termination codons (PTC). The strength of the NMD response appears to reflect multiple determinants on a target mRNA. We have previously reported that mRNAs containing PTCs in close proximity to the translation initiation codon (AUG-proximal PTCs) can substantially evade NMD. Here, we exp...


Nonsense-mediated decay resistance of AUG-proximal nonsense-mutated transcripts...

Peixeiro, Isabel; Barbosa, Cristina; Silva, Ana Luísa; Romão, Luísa

The nonsense-mediated decay (NMD) is a surveillance mechanism that recognizes and rapidly degrades transcripts bearing a premature termination codon (PTC). Although in mammals the location of a PTC more than 50 nucleotides upstream the terminal exonexon junction has been pointed as a mark for NMD, it is now known that the physical distance between the PTC and cytoplasmic poly(A)-binding protein 1 (PABPC1) is a ...


The role of mRNA translation on nonsense-mediated decay inhibition in disorders...

Peixeiro, Isabel; Barbosa, Crsitina; Silva, Ana Luísa; Romão, Luísa

Resumo de apresentação oral


The role of mRNA translation on nonsense-mediated decay inhibition of transcrip...

Peixeiro, Isabel Cristina Ramos, 1982-

Tese de doutoramento, Bioquímica (Genética Molecular), Universidade de Lisboa, Faculdade de Ciências, 2012 ; Nonsense-mediated mRNA decay (NMD) is a surveillance pathway that recognizes and rapidly degrades mRNAs containing premature termination codons (PTC). The unified model for NMD, proposes that the decision of NMD triggering is the outcome of the competition between the cytoplasmatic poly(A)-binding prote...


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