PT  - JOURNAL ARTICLE
AU  - Danielle L Blackwell
AU  - Sherri D Fraser
AU  - Oana Caluseriu
AU  - Claudia Vivori
AU  - Paul MK Gordon
AU  - Amanda V Tyndall
AU  - Ryan E Lamont
AU  - Jillian S Parboosingh
AU  - A Micheil Innes
AU  - François P Bernier
AU  - Sarah J Childs
TI  - Hnrnpul1 loss of function affects skeletal and limb development
AID  - 10.1101/2020.02.04.934257
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.02.04.934257
4099  - http://biorxiv.org/content/early/2020/02/04/2020.02.04.934257.short
4100  - http://biorxiv.org/content/early/2020/02/04/2020.02.04.934257.full
AB  - Mutations in RNA binding proteins can lead to pleiotropic phenotypes including craniofacial, skeletal, limb and neurological symptoms. Heterogeneous Nuclear Ribonucleoproteins (hnRNPs) are involved in nucleic acid binding, transcription and splicing through direct binding to DNA and RNA, or through interaction with other proteins in the spliceosome. Here, we show a developmental role for hnrnpul1 in zebrafish fin and craniofacial development, and in adult onset scoliosis. Furthermore, we demonstrate a role of hnrnpul1 in alternative splicing regulation. In two siblings with congenital limb malformations, whole exome sequencing detected a frameshift variant in HNRNPUL1; the developmental role of this gene in humans has not been explored. Our data suggest an important developmental role of hnRNPUL1 in both zebrafish and humans. Although there are differences in phenotypes between species, our data suggests potential conservation of ancient regulatory circuits involving hnRNPUL1 in these phylogenetically distant species.Summary statement A zebrafish model of loss of Hnrnpul1 shows alternative splicing defects and results in limb growth, craniofacial tendon, and skeletal anomalies.