7 documents found, page 1 of 1
Alectinib-induced anemia with acanthocytosis: To proceed or discontinue treatme...
Simões, Filipa; Sequeira, Telma; Rosa, Rita; Desterro, Joana; Almodovar, Maria TeresaALK gene rearrangements are important oncogenic driver alterations in non-small-cell lung cancer and a predictive factor. When present, it enables the use of tyrosine kinase inhibitors, such as Alectinib. This drug can lead to anemia and erythrocyte morphological changes. We present the case of a 72-year-old patient diagnosed with stage IV non-small cell lung cancer treated with Alectinib in the first line. The...
Targeting mRNA processing as an anticancer strategy
Desterro, Joana; Bak-Gordon, Pedro; Carmo-Fonseca, MariaDiscoveries in the past decade have highlighted the potential of mRNA as a therapeutic target for cancer. Specifically, RNA sequencing revealed that, in addition to gene mutations, alterations in mRNA can contribute to the initiation and progression of cancer. Indeed, precursor mRNA processing, which includes the removal of introns by splicing and the formation of 3' ends by cleavage and polyadenylation, is fre...
Pervasive transcription read-through promotes aberrant expression of oncogenes ...
Grosso, Ana Rita; Leite, Ana Paula; Carvalho, Silvia; Ramos De Matos, Mafalda; Martins, Filipa B.; Vítor, Alexandra; Desterro, JoanaAberrant expression of cancer genes and non-canonical RNA species is a hallmark of cancer. However, the mechanisms driving such atypical gene expression programs are incompletely understood. Here, our transcriptional profiling of a cohort of 50 primary clear cell renal cell carcinoma (ccRCC) samples from The Cancer Genome Atlas (TCGA) reveals that transcription read-through beyond the termination site is a sour...
In vivo requirement of the small subunit of U2AF for recognition of a weak 3′ s...
Pacheco, Teresa; Coelho, Miguel B.; Desterro, Joana; Mollet, Inês G.; Carmo-Fonseca, MariaThe U2 snRNP auxiliary factor (U2AF) is an essential splicing factor composed of two subunits, a large, 65-kDa subunit (U2AF(65)) and a small subunit, U2AF(35). U2AF(65) binds to the polypyrimidine tract upstream from the 3' splice site and promotes U2 snRNP binding to the pre-mRNA. Based on in vitro studies, it has been proposed that U2AF(35) plays a role in assisting U2AF(65) recruitment to nonconsensus polyp...
SUMO-1 modification alters ADAR1 editing activity
Desterro, Joana; Keegan, Liam P.; Jaffray, Ellis; Hay, Ron T.; O'Connell, Mary A.; Carmo-Fonseca, MariaWe identify ADAR1, an RNA-editing enzyme with transient nucleolar localization, as a novel substrate for sumoylation. We show that ADAR1 colocalizes with SUMO-1 in a subnucleolar region that is distinct from the fibrillar center, the dense fibrillar component, and the granular component. Our results further show that human ADAR1 is modified by SUMO-1 on lysine residue 418. An arginine substitution of K418 aboli...
Intracellular macromolecular mobility measured by fluorescence recovery after p...
Braga, José; Desterro, Joana; Carmo-Fonseca, MariaFluorescence recovery after photobleaching (FRAP) is a widely used tool for estimating mobility parameters of fluorescently tagged molecules in cells. Despite the widespread use of confocal laser scanning microscopes (CLSMs) to perform photobleaching experiments, quantitative data analysis has been limited by lack of appropriate practical models. Here, we present a new approximate FRAP model for use on any stan...
Dynamic association of RNA-editing enzymes with the nucleolus
Desterro, Joana; Keegan, Liam P.; Lafarga, Miguel; Berciano, Maria Teresa; O'Connell, Mary; Carmo-Fonseca, MariaADAR1 and ADAR2 are editing enzymes that deaminate adenosine to inosine in long double stranded RNA duplexes and specific pre-mRNA transcripts. Here, we show that full-length and N-terminally truncated forms of ADAR1 are simultaneously expressed in HeLa and COS7 cells owing to the usage of alternative starting methionines. Because the N-terminus of ADAR1 contains a nuclear export signal, the full-length protein...