Anti-HNRNPH2 monoclonal antibody, clone FQS23281(C)

p53 is one of the most important tumor suppressor genes, and the exploration of p53-target genes is important for elucidation of its functional mechanisms. In this study, we identified Armadillo Repeat gene deleted in Velo-Cardio-Facial syndrome (ARVCF) as a direct target of p53 through ChIP-sequencing analysis. Activated p53 protein was found to bind to two distinct sites in the ARVCF gene, resulting in induction of ARVCF expression at both the mRNA and protein levels. We revealed that the knockdown of ARVCF inhibited p53-induced apoptosis. Interestingly, ARVCF interacted with hnRNPH2, which is involved in pre-mRNA splicing, and ARVCF knockdown induced dynamic changes in alternative splicing patterns. These results suggest that p53-induced ARVCF indirectly, but not directly, regulates p53 target selectivity through splicing alterations of specific genes. Thus, we demonstrated that the induction of ARVCF expression contributed to the tumor suppressive function of p53. Recently, it has been reported that many tumors have thousands of alternative splicing events that are not detectable in normal samples. ARVCF may play a role in alternative splicing events in cancer and may provide clues to explore novel approaches for cancer diagnosis and therapy.

Via whole-exome sequencing, we identified six females from independent families with a common neurodevelopmental phenotype including developmental delay, intellectual disability, autism, hypotonia, and seizures, all with de novo predicted deleterious variants in the nuclear localization signal of Heterogeneous Nuclear Ribonucleoprotein H2, encoded by HNRNPH2, a gene located on the X chromosome. Many of the females also have seizures, psychiatric co-morbidities, and orthopedic, gastrointestinal, and growth problems as well as common dysmorphic facial features. HNRNPs are a large group of ubiquitous proteins that associate with pre-mRNAs in eukaryotic cells to produce a multitude of alternatively spliced mRNA products during development and play an important role in controlling gene expression. The failure to identify affected males, the severity of the neurodevelopmental phenotype in females, and the essential role of this gene suggests that male conceptuses with these variants may not be viable.