Fig. 9: Model depicting the proposed molecular mechanism underlying HuD regulation by FMRP and mutant FUS.
From: ALS-related FUS mutations alter axon growth in motoneurons and affect HuD/ELAVL4 and FMRP activity
The figure depicts a model of the competition between mutant FUS and FMRP for HuD 3′UTR binding. In FUSWT MNs, the FUS protein is predominantly localized in the nucleus. In the cytoplasm, FMRP binds HuD 3′UTR repressing its translation. NRN1 mRNAs are destabilized. In FUSP525L MNs, mutant FUS is partially delocalized to the cytoplasm and outcompetes FMRP binding on the HuD 3′UTR. As a consequence, increased HuD protein levels accumulate in FUS mutant MNs. HuD binding to NRN1 and GAP43 3′UTR leads to stabilization of these transcripts and higher protein levels. NRN1 increase underlies the aberrant axonal growth phenotypes.
