In silico Characterization of Human Prion-Like Proteins: Beyond Neurological Diseases

Iglesias V , Paladin L , Juan-Blanco T , Pallarès I , Aloy P , Tosatto S , Ventura S,
Frontiers in Physiology, 2019

Prion-like behavior has been in the spotlight since it was first associated with the
onset of mammalian neurodegenerative diseases. However, a growing body of evidence
suggests that this mechanism could be behind the regulation of processes such
as transcription and translation in multiple species. Here, we perform a stringent
computational survey to identify prion-like proteins in the human proteome. We detected
242 candidate polypeptides and computationally assessed their function, protein–
protein interaction networks, tissular expression, and their link to disease. Human
prion-like proteins constitute a subset of modular polypeptides broadly expressed
across different cell types and tissues, significantly associated with disease, embedded
in highly connected interaction networks, and involved in the flow of genetic information
in the cell. Our analysis suggests that these proteins might play a relevant role not only
in neurological disorders, but also in different types of cancer and viral infections.