PUBLICATION
Hnrnpul1 controls transcription, splicing, and modulates skeletal and limb development in vivo
- Authors
- Blackwell, D.L., Fraser, S.D., Caluseriu, O., Vivori, C., Tyndall, A.V., Lamont, R.E., Parboosingh, J.S., Innes, A.M., Bernier, F.P., Childs, S.J.
- ID
- ZDB-PUB-220325-12
- Date
- 2022
- Source
- G3 (Bethesda) 12(5): (Journal)
- Registered Authors
- Childs, Sarah J., Lamont, Ryan
- Keywords
- Alternative splicing, Craniofacial, Hnrnpul1, Limb, Scoliosis, Zebrafish
- Datasets
- GEO:GSE144754
- MeSH Terms
-
- Alternative Splicing
- Animals
- Heterogeneous-Nuclear Ribonucleoproteins/genetics
- RNA/metabolism
- RNA Splicing*/genetics
- Zebrafish*/genetics
- Zebrafish*/metabolism
- PubMed
- 35325113 Full text @ G3 (Bethesda)
Citation
Blackwell, D.L., Fraser, S.D., Caluseriu, O., Vivori, C., Tyndall, A.V., Lamont, R.E., Parboosingh, J.S., Innes, A.M., Bernier, F.P., Childs, S.J. (2022) Hnrnpul1 controls transcription, splicing, and modulates skeletal and limb development in vivo. G3 (Bethesda). 12(5):.
Abstract
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. We show a developmental role for Hnrnpul1 in zebrafish, resulting in reduced body and fin growth and missing bones. Defects in craniofacial tendon growth and adult-onset caudal scoliosis are also seen. We demonstrate a role for Hnrnpul1 in alternative splicing and transcriptional regulation using RNA sequencing, particularly of genes involved in translation, ubiquitination, and DNA damage. Given its cross-species conservation and role in splicing, it would not be surprising if it had a role in human development. Whole exome sequencing detected a homozygous frameshift variant in HNRNPUL1 in two siblings with congenital limb malformations, which is a candidate gene for their limb malformations. Zebrafish Hnrnpul1 mutants suggest an important developmental role of hnRNPUL1 and provide motivation for exploring potential conservation of ancient regulatory circuits involving hnRNPUL1 in human development.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping