Post transcriptional control of SMN2 expression
Role of the U2AF65 splicing factor in mRNA regulatory networks
RNA regulation in the somite clock
The formation of somites, during embryonic development, is highly regulated both temporally and spatially. The main effectors of this regulation are a set of cyclic genes, that display an oscillating pattern of expression, and a morphogenetic gradient, which constitutes the wavefront of differentiation. Wilts the oscillating behavior of the cyclic genes requires a certain instability at the mRNA level, the wavefront gradient is formed by the slow degradation of mRNA. Our aim is the study and characterization of the mechanisms that regulate mRNA stability in this context. Using Zebrafish as a model organism, we are combining bioinformatic and biochemical approaches with in vivo studies.
small RNAs in HIV infection
HIV infection occurs following a series of virus-host interactions that culminate in the integration of viral DNA into the host cell genome. This process results in the generation of a pool of latently infected CD4 T cells, resistant to therapies that target replicating viruses, and constitutes a major viral reservoir. It is hoped that drugs that prevent the establishment of this pool, such as Raltegravir, may help to address this problem. Regulatory small non-coding RNAs are likely to impact on the molecular processes of the HIV life-cycle particularly through the regulation of the cellular pathways of T cell activation. With this reasoning we have performed a deep-sequencing analysis of the profile of small RNA expression in primary human naïve CD4 T cells, and upon T cell activation and HIV infection. Our preliminary data showed a differential expression of miRNAs upon cell activation, and/or HIV infection, which is modulated by Raltegravir. Our results also supported the hypothesis that some miRNAs are distinctly modulated by HIV-1 and HIV-2 and may potentially be implicated in their distinct levels of replication and/or latency. Lastly, our preliminary results show that HIV-1 and HIV-2 infection induces significant changes of other small RNAs, which we are currently investigating. This project is being developed in collaboration with the Clinical Immunology Unit (PI: Ana E. Sousa) and the Retroviruses and Antiviral Research Unit (PI: João Gonçalves) at the Institute of Molecular Medicine, University of Lisbon. This project is being supported by Merck Investigator-Initiated Studies Program (IISP).