Gene regulation by Y-box proteins: coupling control of transcription and translation

doi:10.1016/S0962-8924(98)01300-2

Trends in Cell Biology

Volume 8, Issue 8, 1 August 1998, Pages 318-323

https://doi.org/10.1016/S0962-8924(98)01300-2 Get rights and content

Abstract

Y-box proteins are multifunctional regulators of gene expression. In somatic cells, they have the capacity to exert positive and negative effects on both transcription and translation. In Xenopus oocytes, they help to mask maternal mRNA and couple the transcription of mRNA in the nucleus to its translational fate in the cytoplasm. This review describes how the capacity of the Y-box proteins to destabilize both RNA and DNA duplexes, together with their distribution between nuclear and cytoplasmic compartments, might explain these multiple roles.

Section snippets

Y-box protein structure and nucleic acid recognition

Y-box proteins have been characterized in all eukaryotes examined, with the notable exception of Saccharomyces cerevisiae (Table 1). They all contain the CSD, which is an oligosaccharide- or oligonucleotide-binding (OB) structure consisting of a five-stranded β-barrel that includes two RNA-binding sequence motifs RNP1 and RNP2 (Fig. 1a)[24]. Prokaryotic cold-shock proteins, whose structural analysis characterized the CSD, bind selectively to double- and single-stranded DNA sequences24, 25. The

Translational control by Y-box proteins

Messenger RNA in all eukaryotic cells exists as a ribonucleoprotein complex that forms the template for the translational machinery. The two major proteins that bind to mRNA in the cytoplasm of somatic cells are poly-(A)-binding protein and a Y-box protein, previously described as the major core protein of cytoplasmic messenger ribonucleoprotein particles (p50)34, 35. The mammalian Y-box proteins (see Table 1) are all practically identical in sequence (>96%). Their properties appear to be

Transcriptional control by Y-box proteins

Y-box proteins were defined initially by their selective association with the duplex Y-box sequence (CTGATTGGCCAA) found in the major histocompatibility complex (MHC) class II genes2, 35. Prokaryotic cold-shock proteins associate selectively with one strand of this sequence25, 26and can stimulate transcription from a promoter in which it is found[40]. Y-box proteins activate transcription from the Xenopus hsp70 promoter and from the herpes simplex virus thymidine kinase promoter in vitro[40]and

Coupling transcription and translation in Xenopus oocytes

Nature often uses the same protein for multiple tasks. Several transcription factors also function as RNA-binding proteins44, 45. Although the acquisition of diverse roles by a single protein is often opportunistic, shared functions might also serve physiologically relevant roles. Y-box proteins can influence both transcription and translation, and so they provide an opportunity to link events in the nucleus to those in the cytoplasm. An example of such a novel regulatory function is shown by

Are the functions of the Y-box proteins in Xenopus oocytes dependent on phosphorylation?

The Y-box protein FRGY2 is modified by phosphorylation[49]. A casein kinase II activity found in oocytes in association with masked RNPs modifies serine/threonine residues in the tail domains of FRGY2[50]. Phosphorylation facilitates photocrosslinking of FRGY2 to mRNA and potentiates repression of translation by FRGY2 in an in vitro reaction49, 50. It has been suggested that phosphorylation of the tail domain facilitates protein–protein interactions between adjacent FRGY2 molecules bound to mRNA

Physiological roles of Y-box proteins

The Y-box proteins of somatic cells might have a role in promoting cell proliferation13, 14, 51. This hypothesis is based on the correlation between growth and transformation and the upregulation of YB-1 in actively dividing cells and the presence of Y-box elements in the promoters of several genes whose activity is associated with cell division13, 14, 51. In addition, since Y-box proteins show tissue-specific patterns of expression, specialized regulatory functions cannot be excluded[52].

Future prospects

Research on both transcription and translation has revealed roles for the Y-box proteins in gene expression. In both instances, the capacity of these proteins to destabilize the structure of duplex DNA and RNA towards a single-stranded form provides a potential mechanism for Y-box protein function. This activity is conferred by the highly conserved CSD. Any effect of the Y-box protein will depend on the context in which function is assayed since the same protein can activate and repress both

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Cell cycle arrest plays critical roles in preventing renal tubular epithelial cell (RTEC) injury and maladaptation after the onset of chronic kidney disease (CKD), but the underlying mechanism governing this arrest has not been fully elucidated. This study was designed to determine the underlying role of YB-1 in promoting cell cycle progression and nuclear translocation in HK-2 cells induced by trimethylamine N-oxide (TMAO).
YB-1 primarily accumulated in the cytoplasm in HK-2 cells after they were treated with TMAO for 30 min and 6 h. Gene expression was analysed using RNA sequencing in HK-2 cells treated with TMAO. Cell cycle progression was analysed via flow cytometry. Luciferase assay and ChIP-PCR were performed to determine the relationship between transcription factor YB-1 and Gadd45a promoter region. Additionally, mice were fed with TMAO to test renal dysfunction and measure the expression of YB-1, GADD45a and CCNA2 in the kidney sections through immunohistochemistry.
YB-1 primarily accumulated in the cytoplasm in HK-2 cells after they were treated with TMAO for 30 min and 6 h. RNA sequencing analysis showed that the cell cycle checkpoint genes growth arrest and DNA damage (Gadd)45a, Gadd45g, cyclin (Ccn)a2, Ccnb1, Ccne1 and Ccnf were differentially expressed in HK-2 cells after treated with 400 μM TMAO for 30 min. Flow cytometry results demonstrated that cell cycle progression was blocked at the G2/M checkpoint. In animal models, elevated dietary TMAO directly led to progressive renal tubulointerstitial dysfunction and inhibited the expression of YB-1 in kidney. Moreover, YB-1 was determined to regulate Gadd45a expression by directly binding to its promoter region. YB-1 expression was negatively correlated with the expression of Gadd45a and Gadd45g but positively correlated with Ccna2, Ccnb1, Ccne1 and Ccnf in CKD.
YB-1 may be a reliable molecular target and an effective prognostic biomarker for CKD.
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The aim of the study was to explore the effect of cold shock treatment on quality and relative expression of cold shock domain proteins (CSDPs) in sweet cherry fruits. The sweet cherry fruits were immersed in 0 °C ice water (ice : water = 1:1 w/v) for 10 min, then were stored at 0 ± 1 °C and 90 % relative humidity (RH) in the dark. The results showed that cold shock treatment not only reduced the weight loss and inhibited the accumulation of malondialdehyde (MDA) of the sweet cherry fruits, but also maintained some other indicators like firmness, H* values, chroma values, and total anthocyanin content. The quality of sweet cherries treated with cold shock was better than that of the control. Moreover, the cold shock treatment reduced the expression of CSDP2, but induced the expression of CSDP3. Interestingly, the cold shock treatment did not have much impact on the expression of CSDP1 and CSDP4. The study showed that cold shock treatment could maintain the quality and induced the relative expression of CSDPs in sweet cherry fruits, which may be a potential approach for reducing the loss of postharvest sweet cherry.
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Citation Excerpt :
These results indicated that compared with YB-1, BAF60a serves as a major effector responsive for physiological nutrient changes, and the BAF60a/YB-1 complex synergistically functions to produce the inhibitory effects on the metabolic processes, such as ureagenesis. Nevertheless, YB-1 participates in a wide variety of DNA/RNA-dependent events, including DNA reparation, pre-mRNA transcription and splicing, mRNA packaging, and regulation of mRNA stability and translation [38–40]. Therefore, it is of particular interest to explore whether these events are also involved in BAF60a-YB-1 complex-induced repression of the CPS1 expression.
Ureagenesis predominantly occurs in the liver and functions to remove ammonia, and the dysregulation of ureagenesis leads to the development of hyperammonemia. Recent studies have shown that ureagenesis is under the control of nutrient signals, but the mechanism remains elusive. Therefore, intensive investigation of the molecular mechanism underlying ureagenesis will shed some light on the pathology of metabolic diseases related to ammonia imbalance.
Mice were fasted for 24 h or fed a high-fat diet (HFD) for 16 weeks. For human evaluation, we obtained a public data set including 41 obese patients with and without hepatic steatosis. We analyzed the expression levels of hepatic BAF60a under different nutrient status. The impact of BAF60a on ureagenesis and hyperammonemia was assessed by using gain- and loss-of-function strategies. The molecular chaperons mediating the effects of BAF60a on ureagenesis were validated by molecular biological strategies.
BAF60a was induced in the liver of both fasted and HFD-fed mice and was positively correlated with body mass index in obese patients. Liver-specific overexpression of BAF60a inhibited hepatic ureagenesis, leading to the increase of serum ammonia levels. Mechanistically, BAF60a repressed the transcription of Cps1, a rate-limiting enzyme, through interaction with Y-box protein 1 (YB-1) and by switching the chromatin structure of Cps1 promoter into an inhibitory state. More importantly, in response to different nutrient status, PGC-1α (as a transcriptional coactivator) and YB-1 competitively bound to BAF60a, thus selectively regulating hepatic fatty acid β-oxidation and ureagenesis.
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YBX3 itself has been reported to control gene expression at multiple levels. It was first reported as a DNA-binding factor that regulates the transcription of promoters containing a YBX sequence (Coles et al., 1996; Kudo et al., 1995; Matsumoto and Wolffe, 1998; Sakura et al., 1988; Wolffe and Meric, 1996). Later reports established YBX3 as an RNA-binding protein (RBP) that post-transcriptionally controls translation and mRNA stability (Coles et al., 2004; Davies et al., 2000; Giorgini et al., 2001; Nie et al., 2012).
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One of the challenges of sturgeon aquaculture is that sturgeon takes an extended amount of time to reach sexual maturity. The pattern of the protein expression in relation to the late maturity of sturgeon can help to better understand changes in sexual maturity. 17β-estradiol (E2), testosterone (T) and vitellogenin (Vtg) levels were examined at all stages of sexual maturation in Sterlet sturgeon (Acipenser ruthenus). Two-dimensional gel electrophoresis and mass spectrometry analysis were used to show the pattern of the ovarian proteins. The T levels increased from the previtellogenic to the postvitellogenic stages (P < 0.05) and Vtg showed a decremental pattern in pre- and postvitellogenic, and atresia (not significantly). The analysis showed 900 protein spots, 19 of which were successfully identified and had significant differences between the previtellogenic and the vitellogenic groups (P < 0.05). Among the identified proteins, 40% involved in cell defense (heat shock protein, Glutathione peroxidase, natural killer enhancing factor, peroxiredoxin-2), 30% in transcription and translation (constitutive photomorphogenesis 9 and Ybx2), 20% in metabolism and energy production (triose-phosphate isomerase (TPI)) and 10% in transport (glycolipid transfer protein). In the vitellogenic stage, the proteins were related to metabolism and energy production (TPI, ES1, creatin kinase, enolase, nucleoside diphosphate kinase, 50%), cell defense (thioredoxin and dislophid isomerase, 20%) and transport (fatty acid binding protein, 10%). Our findings show changes in protein expression pattern from cell defense to metabolism during egg development.

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Trends in Cell Biology

Gene regulation by Y-box proteins: coupling control of transcription and translation

Abstract

Section snippets

Y-box protein structure and nucleic acid recognition

Translational control by Y-box proteins

Transcriptional control by Y-box proteins

Coupling transcription and translation in Xenopus oocytes

Are the functions of the Y-box proteins in Xenopus oocytes dependent on phosphorylation?

Physiological roles of Y-box proteins

Future prospects

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