Like secret agents on a special mission, they have found the right key to enter in a secret location and do something before something bad happens. The agents are ten researchers from the universities of Trento and Washington. Their mission: to block the development of tumor cells.
The study was recently published in the scientific journal “Nature Chemical Biology”. For the first time, the researchers have created an engineered protein (from the Rbfox family) that can bind to a specific type of nucleic acid (miR-21, which is involved in the development of tumor cells) like a key matches a lock, and that, once inside the tumor cell, can stop its development. The findings are the result of an international collaboration between the laboratory led by Paolo Macchi (Laboratory of Molecular and Cellular Neurobiology at the Center for Integrative Biology - CIBIO, University of Trento) and the laboratory led by Gabriele Varani (Department of Chemistry, Washington University).
“The interactions between proteins and nucleic acids (RNA in particular) - explains Paolo Macchi of CIBIO - are very complex. Understanding their functioning and mechanisms helps us create, for example, engineered molecules with new biological features that can be used for research purposes but also to devise new therapies”.
Micro-RNA (or simply miRNA) - continues Macchi - are short RNA sequences that regulate gene activity and play a role in the normal cell development and functioning. In recent years miRNAs have been studied in the context of diseases, like cancer. An altered expression of miRNAs triggers a series of events that lead to cell neoplastic transformations and metastases, therefore to negative outcomes for oncology patients. “In this context, miR-21 is one of the more studied miRNAs because high levels of miR-21 increase the expression of cancer-promoting genes and decrease cancer suppressors”.
Macchi says that his colleagues at the University of Washington, who take a chemical-structural approach to life sciences, contacted the CIBIO biologists for their expertise in cell biology. “This work - he underlines - is important because it enhances once again the value and possible applications of basic research. Thanks to basic research we know the structure of some regions of the proteins that interact with nucleic acids, and we have learned about miRNAs and their involvement in physiological and pathological functions. Sharing the expertise and knowledge of our teams, with their different skills in the various branches of biology, was a very interesting and stimulating experience, and a successful one. This is the second collaborative effort between our two groups that results in a publication in an international journal in just a few months”.
The paper, “Targeted inhibition of oncogenic miR-21 maturation with designed RNA-binding proteins”, was published in the scientific journal “Nature Chemical Biology”. The paper was authored by ten researchers. For the University of Washington: Yu Chen, Fan Yang, Tom Pavelitz, Wen Yang, Katherine Godin, Matthew Walker and Suxin Zheng with the head of laboratory Gabriele Varani; the authors from the University of Trento are Lorena Zubovic and Paolo Macchi, head of the Laboratory of Molecular and Cellular Neurobiology.
The research was funded by the US National Institutes of Health (Grant 1R01 GM103834) and the University of Trento (Progetto Biotecnologie).