As nascent messenger RNA (mRNA) is transcribed, it becomes associated with a variety of proteins, collectively termed heterogeneous nuclear ribonucleoproteins (hnRNPs) that will accompany the mRNA transcript through its lifecycle. HnRNPs play critical roles in all aspects of mRNA metabolism and function. From the regulation of transcription to splicing, transport, localization, and stability, these proteins are essential for proper regulation of gene expression. HnRNP A1, a member of the hnRNP A/B family, is one of the best studied hnRNPs (Bekenstein and Soreq 2013; Jean-Philippe et al. 2013). Here, we review the structure and diverse molecular functions of hnRNP A1, with particular emphasis on its involvement in human diseases.
Historically, the presence of cytoplasmic granules and fibrils in basophilic cells has been initially demonstrated using electron microscopy studies (Porter 1954;...
KeywordsToxicity Dementia Glycine Electrophoresis Oligomer
The authors are grateful to all of our group members who contributed to the interest in hnRNP A1 and to the work involved. This study was supported by the Israeli Ministry of Science Aging program (to H.S) and by the NIH (F32-NS084667 to A.B.). We apologize to any colleagues whose work could not be covered due to space limitations.
- Buratti E, Brindisi A, Giombi M, Tisminetzky S, Ayala YM, Baralle FE. TDP-43 binds heterogeneous nuclear ribonucleoprotein A/B through its C-terminal tail: an important region for the inhibition of cystic fibrosis transmembrane conductance regulator exon 9 splicing. J Biol Chem. 2005;280:37572–84. doi: 10.1074/jbc.M505557200.CrossRefPubMedGoogle Scholar
- Cheunim T, Zhang J, Milligan SG, McPhillips MG, Graham SV. The alternative splicing factor hnRNP A1 is up-regulated during virus-infected epithelial cell differentiation and binds the human papillomavirus type 16 late regulatory element. Virus Res. 2008;131:189–98. doi: 10.1016/j.virusres.2007.09.006.CrossRefPubMedPubMedCentralGoogle Scholar
- Douglas JN, Gardner LA, Salapa HE, Lalor SJ, Lee S, Segal BM, et al. Antibodies to the RNA-binding protein hnRNP A1 contribute to neurodegeneration in a model of central nervous system autoimmune inflammatory disease. J Neuroinflammation. 2016;13:178. doi: 10.1186/s12974-016-0647-y.CrossRefPubMedPubMedCentralGoogle Scholar
- Kim S, Merrill BM, Rajpurohit R, Kumar A, Stone KL, Papov VV, et al. Identification of N(G)-methylarginine residues in human heterogeneous RNP protein A1: Phe/Gly-Gly-Gly-Arg-Gly-Gly-Gly/Phe is a preferred recognition motif. Biochemistry. 1997;36:5185–92. doi: 10.1021/bi9625509.CrossRefPubMedGoogle Scholar
- Le Ber I, Van Bortel I, Nicolas G, Bouya-Ahmed K, Camuzat A, Wallon D, et al. hnRNPA2B1 and hnRNPA1 mutations are rare in patients with "multisystem proteinopathy" and frontotemporal lobar degeneration phenotypes. Neurobiol Aging. 2014;35:934 e5–6. doi: 10.1016/j.neurobiolaging.2013.09.016.CrossRefGoogle Scholar
- Nadler SG, Merrill BM, Roberts WJ, Keating KM, Lisbin MJ, Barnett SF, et al. Interactions of the A1 heterogeneous nuclear ribonucleoprotein and its proteolytic derivative, UP1, with RNA and DNA: evidence for multiple RNA binding domains and salt-dependent binding mode transitions. Biochemistry. 1991;30:2968–76.CrossRefPubMedGoogle Scholar
- Shi Y, Frost PJ, Hoang BQ, Benavides A, Sharma S, Gera JF, et al. IL-6-induced stimulation of c-myc translation in multiple myeloma cells is mediated by myc internal ribosome entry site function and the RNA-binding protein, hnRNP A1. Cancer Res. 2008;68:10215–22. doi: 10.1158/0008-5472.CAN-08-1066.CrossRefPubMedPubMedCentralGoogle Scholar
- Ting NS, Pohorelic B, Yu Y, Lees-Miller SP, Beattie TL. The human telomerase RNA component, hTR, activates the DNA-dependent protein kinase to phosphorylate heterogeneous nuclear ribonucleoprotein A1. Nucleic Acids Res. 2009;37:6105–15. doi: 10.1093/nar/gkp636.CrossRefPubMedPubMedCentralGoogle Scholar
- Villarroya-Beltri C, Gutierrez-Vazquez C, Sanchez-Cabo F, Perez-Hernandez D, Vazquez J, Martin-Cofreces N, et al. Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs. Nat Commun. 2013;4:2980. doi: 10.1038/ncomms3980.CrossRefPubMedPubMedCentralGoogle Scholar