Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.27.174136v1?rss=1 Authors: Greenblatt, E. J., Spradling, A. C. Abstract: Mutations in Fmr1 are the leading heritable cause of intellectual disability and autism spectrum disorder. We previously found that Fmr1 acts as a ~2-fold activator of translation of large proteins in Drosophila oocytes, in contrast to its proposed role as a repressor of translation elongation. Here, we show that genes associated with autism spectrum disorders tend to be dosage-sensitive and encode proteins that are larger than average. Reanalysis of Fmr1 KO mouse cortex ribosome profiling data demonstrates that autism-associated mRNAs encoding large proteins exhibit a concordant reduction in ribosome footprints, consistent with a general role for Fmr1 as a translational activator. We find no evidence that differential ribosomal pausing affects translational output in Fmr1-deficient Drosophila oocytes or mouse cortex. Furthermore, long Fmr1 target transcripts are preferentially enriched in stress granules upon acute stress. Our data thus identify a critical role for Fmr1 in promoting the translation of long, stress-sensitive, autism-associated mRNAs. Copy rights belong to original authors. Visit the link for more info