TY  - GEN
T1  - sym-2 loss-of-function causes glutamatergic neurodegeneration after oxidative stress
AU  - Ryan, Veronica H.
AU  - Hart, Anne C.
DO  - 10.17912/micropub.biology.000363
UR  - http://beta.micropublication.org/journals/biology/micropub-biology-000363/
AB  - sym-2 encodes an ortholog of the RNA-binding proteins hnRNPF and hnRNPH. A putative loss-of-function allele, sym-2(mn617) from (Davies et al., 1999) is a Y163N missense mutation, which lies N-terminal to the first RNA-recognition motif of SYM-2. Homozygous animals have no overt defects but animals heterozygous for sym-2(mn617) and homozygous for mec-8 mutations are embryonic lethal (Davies et al., 1999; Yochem et al., 2004). Additionally, sym-2(mn617) suppresses the exhaustion-induced locomotion defect of smn-1(cb131) animals (Walsh et al., 2020). We have previously shown that human hnRNPA2, an ortholog of the protein encoded by C. elegans hrpa-1, interacts with hnRNPF in vitro (Ryan et al., 2020). As the low complexity (LC) domains of hnRNPA2 and HRPA-1 are not well conserved, we replaced the third coding exon of the C. elegans hrpa-1 gene with the corresponding human protein sequence codon optimized for C. elegans expression, resulting in a chimeric HRPA-1 protein with the human LC domain (HRPA-1HsLCWT) (Ryan et al., 2020). A mutation in hnRNPA2, D290V, is associated with multisystem proteinopathy, a disease that causes degeneration of muscles, bone, and neurons (Kim et al., 2013). Expression of the mutant chimeric version of hrpa-1, hrpa-1HsLCD290V, causes glutamatergic neurodegeneration in phasmid neurons after oxidative stress in animals lacking endogenous hrpa-1 function (Ryan et al., 2020). To control for defects associated with array integration, we also created an empty array, hrpa-1HsLCempty, which contains no hrpa-1. We hypothesized that sym-2(mn617) might rescue hrpa-1HsLCD290V stress-induced neurodegeneration.
PY  - 2021
JO  - microPublication Biology
ER  -