Browsing by Author "Gama Carvalho, Margarida"
Now showing 1 - 2 of 2
Results Per Page
Sort Options
- How the DIS3 proteins shape the human transcritpomePublication . Costa, Paulo; Santos, Hugo; Gama Carvalho, Margarida; Romão, LuísaThe final step of eukaryotic mRNA degradation proceeds in either a 5’-3’ direction, catalyzed by XRN1, or in a 3’-5’ direction catalyzed by DIS3, DIS3L1 (the catalytic subunits of the exosome) and/or DIS3L2 (exosome-independent). Important findings over the last years have shed a new light onto the mechanistic details of RNA degradation by these exoribonucleases. In addition, it has been shown that they are involved in growth, mitotic control and important human diseases, including cancer. With the aim of analyzing how DIS3, DIS3L1 and DIS3L2 regulate the human transcriptome, each one of these nucleases was depleted by RNA interference in HeLa cells and levels of several reporter mRNAs was monitored by RT-qPCR. Our results show that these exoribonucleases are target specific and not directly involved in a particular mRNA surveillance mechanism. In parallel, our bioinformatics analysis of available transcriptomic data from cells depleted of DIS3L1, DIS3L2, XRN1, or UPF1 (which has a central role in nonsense-mediated mRNA decay) has shown some, but not full, redundancy among the transcripts regulated by these nucleases, which supports our experimental data. Presently, we are exploring the molecular mechanisms underlying our observations.
- Upregulation of RAC1/PAK1 signalling promotes DNA damage repair in colorectal cancer cellsPublication . Barros, Patricia; Amaral, Andreia; Abrantes, Leonor; Oliveira, Tiago; Louro, Henriqueta; Silva, Maria Joâo; Jordan, Peter; Gama Carvalho, Margarida; Matos, PauloIntroduction: Colorectal cancer is one of the most prevalent types of cancer worldwide. The GTPase RAC1 and its effector PAK1 have been found overexpressed or hyperactivated in this type of cancers, particularly those with more aggressive and invasive features, which is frequently correlated with resistance to chemotherapeutics and unfavourable clinical prognosis. Previously, we described a new signalling pathway in which activation of RAC1/PAK1 signalling promotes a transcriptional switch between the BCL6 repressor and the STAT5 transcriptional activator at a restricted subset of gene promoters.