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Among the various cis-acting elements in mRNAs that participate in regulating protein synthesis are AUG codons within transcript leader sequences (uAUGs) and, in some cases, associated short upstream open reading frames (uORFs). Although about 15% of the human mRNAs present uORFs (mainly, those transcripts encoding growth factors or hormones), there is no general model for the mechanism by how and when an uORF downregulates the main ORF expression. Leaky scanning and reinitiation are mechanisms that allow translational control of the main ORF in a transcript bearing at least one uORF. In the leaky scanning mechanism ribosomes either ignore the uAUG codon and scan past it or recognize it, initiating translation. Short regulatory uORFs may also permit the small ribosomal subunit to stay mRNA-bound after termination and resume scanning fo...
Among the various cis-acting elements present in the 5’ leader sequence of mRNAs there are upstream open reading frames (uORFs). Although their function is still poorly understood, they are known to downregulate the main ORF expression of several human transcripts that code for key regulatory genes. The human erythropoietin (EPO) is a glycoprotein that was initially characterized has a hormone mainly synthesized and released from the kidney, with a key role in hematopoiesis. However, many recent reports have implicated EPO in several non-hematopoietic functions and have shown its production in several other organs. Consequently, it might be used as a therapeutic target for the treatment of several human disorders. We found a natural occurring 14-codon-uORF on the human EPO transcript. Our belief is that understanding the molecular me...
Among the various cis-acting elements present in the 5’ leader sequence of mRNAs there are upstream open reading frames (uORFs). Although their function is still poorly understood, they are known to downregulate the main ORF expression of several human transcripts that code for key regulatory genes. The human erythropoietin (EPO) is a glycoprotein that was initially characterized has a hormone mainly synthesized and released from the kidney, with a key role in hematopoiesis. However, many recent reports have implicated EPO in several non-hematopoietic functions and have shown its production in several other organs. Consequently, it might be used as a therapeutic target for the treatment of several human disorders. We found a natural occurring 14-codon-uORF on the human EPO transcript. Our belief is that understanding the molecular mech...
Erythropoietin (EPO) is a key mediator hormone for hypoxic induction of erythropoiesis that also plays important nonhematopoietic functions. It has been shown that EPO gene expression regulation occurs at different levels, including transcription and mRNA stabilization. In this report, we show that expression of EPO is also regulated at the translational level by an upstream open reading frame (uORF) of 14 codons. As judged by comparisons of protein and mRNA levels, the uORF acts as a cis-acting element that represses translation of the main EPO ORF in unstressed HEK293, HepG2, and HeLa cells. However, in response to hypoxia, this repression is significantly released, specifically in HeLa cells, through a mechanism that involves processive scanning of ribosomes from the 5' end of the EPO transcript and enhanced ribosome bypass of the u...
Dissertação submetida como requisito parcial para obtenção do grau de Mestre em Economia e Políticas Públicas
Biblioteca centralPalácio Ceia
Rua da Escola Politécnica, nº 141 - 147
1269-001 Lisboa, Portugal

Telefones: (+351) 300 002 922
(+351) 300 002 925 | (+351) 300 002 930
(+351) 300 002 931 | (+351) 300 002 932
Correio eletrónico: cdoc@uab.pt

Horário de atendimento:
Segunda a sexta, das 9h às 18h
Delegação de CoimbraRua Alexandre Herculano, nº 52
3000-019 Coimbra, Portugal

Telefone: (+351) 300 001 590
Correio eletrónico: cdocoimbra@uab.pt

Horário de atendimento:
Segunda a sexta, das 9h às 12h30 e das 14h às 18h
Delegação do PortoRua de Amial, nº 752
4200-055 Porto, Portugal

Telefone: (+351) 300 001 700
Correio eletrónico: cdocporto@uab.pt

Horário de atendimento:
Segunda a sexta, das 9h às 17h30