Microproteins contribute to evolutionary innovation and cancer
Mar Albà
Professor, Hospital del Mar Research Institute and ICREA
In recent years it has become increasingly clear that many long non-coding RNA contain small ORFs that are translated into microproteins. In an evolutionary context, the translation of these ORFs provides the raw material for the generation of novel functional proteins. This process has been called de novo protein emergence, because the new proteins are not related to previously existing proteins. Our work in yeast has uncovered 97 de novo originated proteins that are, for the most part, not annotated in the databases. Some of these microproteins are over-expressed in stress conditions, and are thus likely to have contributed to adapt to extreme environments. In cancer, the translation of small ORFs from long non-coding RNAs can potentially generate neoantigens that are recognized by the immune system. We have developed a computational pipeline that utilizes sequencing data to identify cancer-specific microproteins, and we have applied it to a large cohort of liver cancer patients. Some of them are shared across different patients and could be useful candidates for the development of novel anti-cancer vaccines.
Mar obtained her PhD at the University of Barcelona in 1997 and a Master in Bioinformatics and Molecular Modeling at the University of London in 1999. She worked as a postdoc in the laboratories of John Hancock (Medical Research Council, UK), on the evolution of amino acid tandem repeats, and of Paul Kellam (University College London), on virus genomics. In 2002 she obtained a tenure-track position at Universitat Pompeu Fabra (UPF, Barcelona) and in 2005 she was appointed ICREA Research Professor at Fundacio IMIM and continues to teach at UPF. She currently leads the Evolutionary Genomics group at GRIB (IMIM-UPF).