Martí, EulàliaEstivill, Xavier, 1955-2016-07-062016-07-062013Martí E, Estivill X. Small non-coding RNAs add complexity to the RNA pathogenic mechanisms in trinucleotide repeat expansion diseases. Frontiers in molecular neuroscience. 2013;6:45. DOI: 10.3389/fnmol.2013.000451662-5099http://hdl.handle.net/10230/27008Trinucleotide-repeat expansion diseases (TREDs) are a group of inherited human genetic disorders normally involving late-onset neurological/neurodegenerative affectation. Trinucleotide-repeat expansions occur in coding and non-coding regions of unique genes that typically result in protein and RNA toxic gain of function, respectively. In polyglutamine (polyQ) disorders caused by an expanded CAG repeat in the coding region of specific genes, neuronal dysfunction has been traditionally linked to the long polyQ stretch. However, a number of evidences suggest a detrimental role of the expanded/mutant mRNA, which may contribute to cell function impairment. In this review we describe the mechanisms of RNA-induced toxicity in TREDs with special focus in small-non-coding RNA pathogenic mechanisms and we summarize and comment on translational approaches targeting the expanded trinucleotide-repeat for disease modifying therapies.application/pdfeng© 2013 Martí and Estivill. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.RNA no missatgersinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.3389/fnmol.2013.00045RNA-toxicityAntisense small RNAmiRNASmall non-coding RNAsTrinucleotide repeat expansioninfo:eu-repo/semantics/openAccess