title: Autoregulatory circuit of human rpL3 expression requires hnRNP H1, NPM and KHSRP.
abstract: Alternative pre-mRNA splicing (AS) is a major mechanism that allows proteomic variability in eukaryotic cells. However, many AS events result in mRNAs containing a premature termination codon, which are degraded by nonsense-mediated mRNA decay (NMD) pathway. We have previously demonstrated that human rpL3 autoregulates its expression through the association of AS with NMD. In fact, overexpression of rpL3 promotes downregulation of canonical splicing and upregulation of alternative splicing that produces an NMD-targeted mRNA isoform. The result of these events is a decreased production of rpL3. We have also identified heterogeneous nuclear ribonucleoprotein (hnRNP) H1 as a splicing factor involved in the regulation of rpL3 alternative splicing and identified its regulatory cis-elements within intron 3 transcript. Here, we report that NPM and KHSRP are two newly identified proteins involved in the regulation of rpL3 gene expression via AS-NMD. We demonstrate that hnRNP H1, KHSRP and NPM can be found associated, and present also in ribonucleoproteins (RNPs) including rpL3 and intron 3 RNA in vivo, and describe protein-protein and RNA-protein interactions. Moreover, our data provide an insight on the crucial role of hnRNP H1 in the regulation of the alternative splicing of the rpL3 gene.
authors.affiliation: Dipartimento di Biochimica e Biotecnologie Mediche, Università Federico II, Napoli, Italy.
authors.forename: Annapina
authors.initials: A
authors.lastname: Russo
authors.forename: Morena
authors.initials: M
authors.lastname: Catillo
authors.forename: Davide
authors.initials: D
authors.lastname: Esposito
authors.forename: Paola
authors.initials: P
authors.lastname: Briata
authors.forename: Concetta
authors.initials: C
authors.lastname: Pietropaolo
authors.forename: Giulia
authors.initials: G
authors.lastname: Russo
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D002460:Cell Line; D034541:Heterogeneous-Nuclear Ribonucleoprotein Group F-H / Q000378:metabolism* / Q000502:physiology; D006706:Homeostasis; D006801:Humans; D007438:Introns; D009687:Nuclear Proteins / Q000378:metabolism* / Q000502:physiology; D000090243:Nucleophosmin; D012322:RNA Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D000090822:Ribosomal Protein L3; D012269:Ribosomal Proteins / Q000235:genetics* / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism* / Q000502:physiology
chemical_list: D034541:Heterogeneous-Nuclear Ribonucleoprotein Group F-H; C105789:KHSRP protein, human; D009687:Nuclear Proteins; D012322:RNA Precursors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C000716547:RPL3 protein, human; D000090822:Ribosomal Protein L3; D012269:Ribosomal Proteins; C000716549:Rpl3 protein, rat; D015534:Trans-Activators; D000090243:Nucleophosmin