HuR–hnRNP interactions and the effect of cellular stress

Abstract

The heterogeneous nuclear ribonucleoproteins (hnRNPs) constitute an important group of RNA-binding proteins (RBPs) that play an active role in post-transcriptional gene regulation. Here, we focus on representative members of the hnRNP group of RBPs, namely hnRNP A1 and hnRNP C1/C2, which participate mainly in RNA splicing, as well as on HuR, a prototype of the AU-rich element-binding proteins (ARE-BP), which has an established role in regulating the stability and translation of target mRNAs. HuR and most hnRNPs are primarily localized in the nucleoplasm, and they can shuttle between the nucleus and the cytoplasm. Herein, we have extended our recently reported findings on the ability of HuR to associate with the immunopurified from mammalian cell extracts hnRNP and mRNP complexes by the application of an anti-HuR antibody that selects HuR-RNP complexes. We find that the protein components precipitated by the anti-HuR antibody are very similar to the hnRNP-HuR complexes reported previously. The in vivo association of HuR and hnRNP proteins is examined in the presence and the absence of thermal stress by confocal microscopy of intact cells and by in situ nuclear matrix preparation. We find notable heat-induced changes of HuR and of hnRNP A1, which exit the nucleus and co-localize to large cytoplasmic foci that represent heat-induced stress granules. The functional implications of HuR-hnRNP interactions in stressed and unstressed cells are discussed.

Expression and Functional Studies on the Noncoding RNA, PRINS

“…The heterogeneous nuclear ribonucleoproteins (hnRNPs) play an active part in post-transcriptional gene regulation, e.g., RNA splicing and regulation of the stability and translation of target mRNAs. Most hnRNPs are primarily localized in the nucleoplasm, and can shuttle between the nucleus and the cytoplasm [35]. …”

Lipoteichoic Acid Isolated from Lactobacillus plantarum Inhibits Melanogenesis in B16F10 Mouse Melanoma Cells

“…hnRNPs include at least 20 discrete hnRNPs that are labeled as hnRNP A through U. These hnRNPs are actively involved in many facets of mRNA metabolism, from transcription to post-transcriptional events and translation (Papadopoulou et al, 2013;Wen et al, 2010). ELAV is another important small family of RBPs that comprises four members: HuR, HuB, HuC, and HuD.…”

“…Both hnRNP A1 and HuR are mainly localized in the nucleoplasm. They regulate the stability and translation of target AREcontaining mRNAs and can shuttle between the nucleus and cytoplasm (Brennan and Steiz, 2001;Papadopoulou et al, 2013). In this study, we focused on hnRNP A1 and HuR which are mRNA stabilizing factors that stabilize ARE-containing mRNAs.…”

“…hnRNPs and ELAV/Hu proteins are representative groups of RBPs (Papadopoulou et al, 2013). First, we performed a RNA Electro Mobility Shift Assay (RNA EMSA) to investigate whether hnRNP A1 and HuR interact with ARE on the 3'-UTR of MITF.…”

Characterization of molecules showing altered expression profile in psoriasis

“…Moreover, silencing of PRINS gene resulted in altered HeLa cell morphology and gene expression alterations, among others in the case of G1P3, an interferon-inducible anti-apoptotic gene 34 . It has been reported that long mRNA-like ncRNAs form complexes with proteins [35][36][37] , and act as regulators of various cellular functions 38 . Therefore we have performed an in vitro binding assay which revealed that PRINS interacts physically with the molecular chaperone protein nucleophosmin (NPM, B23) in HaCaT and normal human epidermal keratinocyte (NHEK) lysates and we were first to describe the upregulation of this protein in psoriasis 39 .…”