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A Comparative Overview of the Role of Human Ribonucleases in Nonsense-Mediated ...

da Costa, Paulo J.; Menezes, Juliane; Guedes, Raquel; Reis, Filipa P.; Teixeira, Alexandre; Saramago, Margarida; Viegas, Sandra C.; Arraiano, Cecília M.

Eukaryotic cells possess surveillance mechanisms that detect and degrade defective transcripts. Aberrant transcripts include mRNAs with a premature termination codon (PTC), targeted by the nonsense-mediated decay (NMD) pathway, and mRNAs lacking a termination codon, targeted by the nonstop decay (NSD) pathway. The eukaryotic exosome, a ribonucleolytic complex, plays a crucial role in mRNA processing and turnove...


A Comparative Overview of the Role of Human Ribonucleases in Nonsense-Mediated ...

da Costa, Paulo J.; Menezes, Juliane; Guedes, Raquel; Reis, Filipa P.; Teixeira, Alexandre; Saramago, Margarida; Viegas, Sandra C.; Arraiano, Cecília M.

Eukaryotic cells possess surveillance mechanisms that detect and degrade defective transcripts. Aberrant transcripts include mRNAs with a premature termination codon (PTC), targeted by the nonsense-mediated decay (NMD) pathway, and mRNAs lacking a termination codon, targeted by the nonstop decay (NSD) pathway. The eukaryotic exosome, a ribonucleolytic complex, plays a crucial role in mRNA processing and turnove...


Non-canonical synthesis of UPF1 protein contributes to its oncogenic role in co...

Lacerda, Rafaela; Menezes, Juliane; Antunes Elias, Adriana; Romão, Luísa

Colorectal cancer (CRC) is the third leading cause worldwide and projections point towards an increase over the next two decades. Gene expression dysregulation of several genes involved in CRC contribute to disease development. The up-frameshift 1 (UPF1) protein plays important roles in several cellular mechanisms and acts as a tumour suppressor in most cancers. However, in CRC, this protein has been described ...


Internal ribosome entry site-mediated translation of UPF1 contributes to its on...

Lacerda, Rafaela; Menezes, Juliane; Elias, Adriana; Romão, Luísa

Colorectal cancer (CRC) is the third cause of death worldwide and projections point towards an increase for the next two decades. Many genes are misregulated in CRC, contributing to the development of the disease. Up-frameshift 1 (UPF1) is involved in many cellular mechanisms such as nonsense-mediated mRNA decay, cell cycle progression, or telomere maintenance and homeostasis. It also works as a tumour suppress...


A iniciação não-canónica da síntese da proteína UPF1 contribui para a sua funçã...

Lacerda, Rafaela; Menezes, Juliane; Antunes Elias, Adriana; Romão, Luísa

O cancro colo-rectal (CCR) é a terceira causa de morte ao nível mundial e as projecções apontam para um aumento durante as próximas duas décadas. A desregulação da expressão de vários genes no CCR contribui para o desenvolvimento da doença. A proteína up-frameshift 1 (UPF1) está envolvida em vários mecanismos celulares e, ao contrário da maioria dos cancros, em que a UPF1 desempenha um papel suppressor de tumor...


Functional characterization of variants in the 5’UTR and promoter of PCSK9 gene

Alves, Ana Catarina; Fernandes, Rafael; Menezes, Juliane; Romão, Luísa; Bourbon, Mafalda

Familial hypercholesterolemia (FH) is the most common genetic disorder conferring an increased cardiovascular risk due to cholesterol accumulation since birth. The majority of patients with FH phenotype have mutations in LDLR, APOB or PCSK9 genes. In about 50% of patients a variant causing disease has not been possible to find. The 5' and 3’ untranslated regions (UTRs) and promoter of these genes is poorly stud...


Functional characterization of variants in the 5’ UTR and promoter of LDLR gene

Alves, Ana Catarina; Menezes, Juliane; Fernandes, Rafael; Romão, Luísa; Bourbon, Mafalda

Background and Aims: Familia lhypercholesterolemia (FH) is the most common genetic disorder conferring an increased cardiovascular risk due to cholesterol accumulation since birth. The majority of patients with FH phenotype have mutations in LDLR, APOB or PCSK9 genes. In about 50% of patients a variant causing disease has not been possible to find. The 5'and 3’untranslated regions (UTRs) and promoter of these g...


O mecanismo alternativo de síntese proteica da proteína UPF1 e a sua relevância...

Lacerda, Rafaela; Menezes, Juliane; Romão, Luísa

A proteína up-frameshift 1 (UPF1) é uma proteína multifacetada, com um papel fundamental em vários mecanismos celulares. É um fator essencial no mecanismo de decaimento rápido de mRNAs aberrantes com codões nonsense (NMD, do inglês nonsense-mediated mRNA decay). É também uma proteína crucial para a progressão da fase S do ciclo celular e manutenção do tamanho e homeostasia dos telómeros, de um modo totalmente i...


Learning from mRNA: the relevance of the tumour suppressor protein UPF1’s inter...

Lacerda, Rafaela; Menezes, Juliane; Romão, Luísa

Crucial in several cellular processes, such as nonsense-mediated mRNA decay, cell cycle progression, and telomere maintenance and homeostasis, Up-frameshift 1 (UPF1) has also been considered a tumour suppressor protein in hepatocellular carcinoma and gastric cancer, as it is underexpressed in the latter and negatively correlated to MALAT1 (long non-coding RNA metastasis-associated lung adenocarcinoma transcript...


UPF1 internal ribosome entry site-mediated translation and its importance in tu...

Lacerda, Rafaela; Menezes, Juliane; Romão, Luísa

Aims: UPF1 internal ribosome entry site-mediated translation and its importance in tumorigenesis; Confirm UPF1 5’ untranslated region (UTR) can mediate internal ribosome entry site (IRES)-mediated translation; Check whether the IRES-dependent translation is maintained under cap-dependent-impairing conditions (hypoxia); Identify the minimal sequence required for IRES-mediated translation; Investigate the biologi...


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