A mistranslation-prone transcriptome underlying polyglutamine expansion diseases

We propose a mechanism underlying polyglutamine (polyQ) repeat expansion diseases, in which the translation of expanded CAG codon repeats leads to translation stress. The stress is generated by depletion of the cognate glutaminyl-tRNA pool, which could cause ribosome frameshifting and lead to mistranslation of transcripts with specific characteristics. Michele Vendruscolo and colleagues propose that polyglutamine repeat expansion diseases could be caused by glutaminyl-tRNA depletion, leading to ribosome frameshifting and mistranslation of transcripts with specific characteristics.