Universidade de Lisboa Repositório da Universidade de Lisboa

Repositório da Universidade de Lisboa >
Faculdade de Ciências (FC) >
FC - Teses de Doutoramento >

Please use this identifier to cite or link to this item: http://hdl.handle.net/10451/1606

Título: Study of the nonsense-mediated decay (NMD) mechanism in the human \03B1-globin mRNA
Autor: Pereira, Francisco José Cabral, 1978-
Orientador: Loison, Luísa Romão, 1963-
Amaral, Margarida, 1958-
Palavras-chave: Genética molecular
Teses de doutoramento
Issue Date: 2009
Resumo: Eukaryotic cells have developed mechanisms to regulate many steps of gene expression, preventing defective protein production and ensuring cell survival. Nonsense-mediated mRNA decay (NMD) is a posttranscriptional surveillance pathway able to recognize and eliminate transcripts encoding truncated proteins. In mammalian cells, mRNAs containing premature translation termination codons (PTCs) placed more than 50-55 nucleotides upstream from the last exon-exon junction are generally committed to NMD. However, transcripts carrying a nonsense codon in this condition, located near the translation initiation codon, have been reported to escape decay. The present work contains the description of a clinical case where a PTC, caused by a single nucleotide deletion in the human -globin mRNA, induces accelerated mRNA degradation. On the other hand, data reveals that stop codons located in the first exon of the -globin transcript fail to induce NMD. This resistance to decay is further downstream extended when compared with the equivalent effect observed in the human -globin mRNA, and this divergence is shown to be mainly determined by the sequence upstream to the PTC and the secondary structure of the open reading frame (ORF). Contrary to -globin, the  globin mRNA allows translation reinitiation at a downstream AUG, after translation of a short ORF. However, NMD inhibition persists even when translation reinitiation is prevented. Results suggest that a less-structured short ORF is more rapidly translated and NMD-antagonistic factors, such as PABPC1, may remain associated with the ribosome when it reaches the stop codon. This work constitutes a basic research development with confirmed and potential scientific diffusion, and contributes with prospective benefits in public health, since its results may provide targets for new therapeutic strategies for genetic disorders caused by PTC-generating mutations.
Descrição: Tese de doutoramento, Biologia (Genética Molecular), 2009, Universidade de Lisboa, Faculdade de Ciências
URI: http://catalogo.ul.pt/F/?func=item-global&doc_library=ULB01&type=03&doc_number=000556096
Appears in Collections:FC - Teses de Doutoramento

Files in This Item:

File Description SizeFormat
17931_ulsd_re344_PhD_dissertation_Francisco_Pereira.pdf2,64 MBAdobe PDFView/Open

Please give feedback about this item
FacebookTwitterDeliciousLinkedInDiggGoogle BookmarksMySpace
Formato BibTex MendeleyEndnote Logotipo do DeGóis 

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.


  © Universidade de Lisboa / SIBUL
Alameda da Universidade | Cidade Universitária | 1649-004 Lisboa | Portugal
Tel. +351 217967624 | Fax +351 217933624 | repositorio@reitoria.ul.pt - Feedback - Statistics
Promotores do RCAAP   Financiadores do RCAAP

Fundação para a Ciência e a Tecnologia Universidade do Minho   Governo Português Ministério da Educação e Ciência PO Sociedade do Conhecimento (POSC) Portal oficial da União Europeia