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. 2015 Mar 9;6:87. doi: 10.3389/fgene.2015.00087

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Copyright © 2015 Szafranski, Abraham and Mekhail.

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.

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Proteins implicated in neurodegenerative diseases are involved in multiple steps of the miRNA biogenesis pathway. TDP-43 and FUS (implicated in ALS and FTLD) interact with Drosha (directly and indirectly respectively) to promote the processing of pri-miRNAs into pre-miRNA. After export, TDP-43 also interacts with dicer to process pre-miRNA into mature miRNA. When miRNA is loaded onto the RISC to be targeted for silencing, it interacts with Ago1. In Drosophila, it was shown that the protein Atx2 (the ortholog of ATXN2, a protein implicated in ALS and SCA2) interacts with Ago1 to promote proper targeting of miRNAs to their mRNA.