Hnrnpul1 controls transcription, splicing, and modulates skeletal and limb development in vivo

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.

NAT10-mediated RNA acetylation enhances HNRNPUL1 mRNA stability to contribute cervical cancer progression

“…Hnrnpul1/early region 1B-associated protein 5 (E1B-AP5) of adenovirus belongs to a heterogeneous nuclear ribonucleoprotein (hnRNP) protein family. It plays essential roles in a wide range of biological processes, including RNA splicing and transcriptional regulation 46 . In addition, hnRNPUL1 regulates cellular functions against DNA damage 47 .…”

The Novel Role of hnRNP UL1 in Human Cell Nucleoli

“…Heterogeneous nuclear ribonucleoprotein U-like protein 1 (hnRNP UL1), also known as adenovirus early region 1B-associated protein 5 (E1B-AP5), has been shown to play a role in transcription mainly by acting as a transcriptional regulator that inhibits gene expression; it also plays a role in splicing by directly binding to DNA and/or RNA or by interacting with other proteins in the spliceosome 4 , 18 . It has also been reported that during cellular arrest, hnRNP UL1 represses the expression of replication-dependent histone genes in a complex with U7 snRNP 29 .…”