Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is an abundant ubiquitously expressed protein with important roles in the regulation of gene expression. hnRNP A1 is involved in transcription as well as the splicing, trafficking, and translation of RNA transcripts. hnRNP A1 binds RNA targets in a sequence specific manner through two N-terminal RNA recognition motifs (RRM) and a C-terminal RGG box RNA binding domain. During transcription hnRNPA1 binds to the promoter of target genes and has been shown to function as both a transcriptional activator and repressor. During the removal of introns hnRNP A1 is present in various splicing complexes and interacts with the essential splicing factor U2AF. hnRNP A1 also contributes to alternative splicing by modulating splice site selection. Once in the cytoplasm hnRNPA1 associates with internal ribosomal entry sites (IRES) of mature mRNA and can both inhibitor enhance translation depending on the cellular context. The diversity of functions for hnRNP A1 in gene expression contributes to its role in a wide variety of human diseases including cancers and neurodegenerative diseases such as Alzheimer’s and multiple sclerosis.
Fujiya et al. identified an interesting interaction between the microRNA-18a and hnRNP A1 (1). They showed microRNA-18a binds to and triggers the degradation of hnRNP A1 which can then lead to apoptosis in colon cancer cells. Using the hnRNP A1 antibody they were able to monitor hnRNP A1 levels to demonstrate its degradation through the autophagolysosomal pathway. The Yeo group at the University of California at San Diego used the hnRNP A1 antibody to perform a genome wide analysis of alternative splicing regulation (2). They depleted hnRNP A1 with siRNA and confirmed knockdown by western blotting with the hnRNP A1 antibody and then performed microarray analysis to identify splicing events that depended on hnRNP A1 activity. Additionally they performed CLIP-Seq with the hnRNP A1 antibody to identified RNA binding sites at many 3’ ends of exons. The study demonstrated the complex and cooperative relationships between hnRNPs and their functions in alternative splicing. In a study of DAZAP1, an abundant RNA-binding protein found in the testes, Lin and Yen used the hnRNP A1 antibody to demonstrate the nuclear colocalization of the two proteins through immunostaining. DAZAP1 and hnRNP A1 were both found in hnRNP particles and indicated a role for DAZAP1 in mRNA transport during spermatogenesis.
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PMIDs
1. 24166503
2. 22574288
3. 16772659