A tRNA-modifying enzyme is identified as essential to produce major protein components of the extracellular environment

The mechanism described by IRB Barcelona researchers played a key role in the evolution from unicellular organisms to more complex forms of life.

The understanding of these processes may have an impact on the treatment of diseases related to extracellular proteins, such as asthma and chronic pulmonary obstructive disease.

The results have been published in the journal Nucleic Acids Research.

All species on earth use almost exactly the same genetic code to produce proteins. And yet many human proteins are very distinct from bacterial ones and these differences contribute to the different properties held by human cells and cells of simpler organisms.

Scientists at IRB Barcelona led by ICREA researcher Dr. Lluís Ribas de Pouplana have identified a tRNA-modifying protein called ADAT as a key player in the production of a group of proteins directed at the extracellular environment. The composition of such proteins is so peculiar that cells require certain functional ‘upgrades’ to produce them, and the main one is revealed in this work.

“Extracellular proteins are essential for cell-cell communication, a central requirement to evolve multicellularity,” explains Dr. Ribas de Pouplana, head of the Gene Translation Laboratory, “it is reasonable to conclude that this RNA modification, which is a prevalent feature of eukaryotic cells, played a role in the emergence of multicellular eukaryotes.”

The project has benefited from collaborations with the groups led by ICREA researcher Dr. Toni Gabaldón (IRB Barcelona), Dr. Eva Novoa (Center for Genomic Regulation), and Dr. Ana pardo-Saganta (CIMA, Navarra).

The role of extracellular proteins in common human diseases

The correct development of tissue and organism functions requires an equilibrium in the proteins present in the cellular external environment. Mucins, which are produced to protect epithelial tissues in most animals, are a group of extracellular proteins that are dependent on ADAT.

Mucin overexpression is a major factor in several human diseases, including pulmonary conditions like asthma and chronic pulmonary obstructive disease. These findings highlight that any disease that depends upon the function of these proteins may potentially be treated by inhibiting ADAT. Research efforts will continue along these lines in the coming years.

Related article:
Human tRNAs with inosine 34 are essential to efficiently translate eukarya-specific low-complexity proteins
Adrian Gabriel Torres, Marta Rodríguez-Escribà, Marina Marcet-Houben, Helaine Graziele Santos Vieira, Noelia Camacho, Helena Catena, Marina Murillo Recio, Àlbert Rafels-Ybern, Oscar Reina, Francisco Miguel Torres, Ana Pardo-Saganta, Toni Gabaldón, Eva Maria Novoa & Lluís Ribas de Pouplana
Nucleic Acids Research (2021) DOI: 10.1093/nar/gkab461

About IRB Barcelona

Created in 2005 by the Generalitat de Catalunya (Government of Catalonia) and University of Barcelona, IRB Barcelona is a Severo Ochoa Centre of Excellence, a seal that was awarded in 2011. The institute is devoted to conducting research of excellence in biomedicine and to transferring results to clinical practice, thus improving people’s quality of life, while simultaneously promoting the training of outstanding researchers, technology transfer, and public communication of science. Its 28 laboratories and eight core facilities address basic questions in biology and are orientated to diseases such as cancer, metastasis, Alzheimer’s, diabetes, and rare conditions. IRB Barcelona is an international centre that hosts 400 employees and more than 30 nationalities. It is located in the Barcelona Science Park. IRB Barcelona is a CERCA center, and a member of the Barcelona Institute of Science and Technology (BIST).