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Abstract Background Single-nucleotide polymorphisms (SNPs) in N6-methyladenosine (m6A) related genetic locus play significant roles in tumorigenesis and development. The expression level of many oncogenes and tumour suppressor genes changed because of m6A-associated SNPs. In addition, the relationship between m6A-SNP and bladder cancer (BCa) has not been well studied. Methods We screened m6A-SNPs in BCa by combining m6A-SNPs data and GWAS-SNPs data. Expression quantitative trait loci (eQTL) and differential expression gene (DEGs) analyses were performed. In ring finger protein, transmembrane 2 (RNFT2), rs3088107 (C > G) was found to have significant eQTL signals and make RNFT2 gene differentially-regulated mostly in BCa. We validated the expression level of RNFT2 in 32 pairs of BCa tissues and eight BCa cell lines by quantitative real-time PCR (qRT-PCR). Functional assays were performed to investigate the role of rs3088107 and RNFT2 in BCa in vitro. Results We identified 673 m6A-SNPs, which were associated with BCa. Of these m6A-SNPs, 221 showed eQTL signals, amongst which, rs3088107 in RNFT2 showed significant eQTL signals. Results of bioinformatic analyses showed that 11 genes with m6A-SNPs had a differential expression level in BCa. RNFT2 was predicted to be significantly up-regulated in BCa. The qRT-PCR results validated that RNFT2 was highly expressed in our own BCa tissues and cell lines. High expression of RNFT2 also indicated a worse overall survival. We also revealed that rs3088107 (C > G) could inhibit the expression and m6A modification of RNFT2 by qRT-PCR, western-blot and m6A-RIP assays. Moreover, the results of functional assays indicated that RNFT2 promoted BCa cell proliferation and migration. Conclusion This research found that m6A-SNPs were associated with oncogene RNFT2 in BCa. Furthermore, m6A-SNPs showed great application potential as a new BCa diagnostic biomarker and prognostic indicator.

Objective To observe the expression changes of RNF6 protein in colorectal laterally spreading tumor (LST) tissues and to discuss its significance. Methods Thirty-three patients with LST, 37 patients with protruded-type colorectal adenoma (PA), and 35 patients with colorectal cancer underwent surgery； the tumor tissues removed during the operation were recorded as LST group, PA group and CRC group, and the normal adjacent mucosal tissues (>5 cm away from the cancer tissue) of colorectal cancer patients were recorded as the Control group. RNF6 protein was detected in each tissue by immunohistochemical staining, and the protein expression, including the positive expression rate and positive degree, was evaluated by semi-quantitative scoring, and the relationships between RNF6 protein expression and clinicopathological parameters of LST patients were analyzed. Results Most of the normal adjacent mucosal tissues were not stained or the staining color was light and the positive area was small, while the RNF6 protein in colorectal cancer tissues was darkly stained, most of them were brownish-yellow granule deposits, and the staining degree of PA tissue and LST tis‐ sue was intermediate between adjacent normal tissue and colorectal cancer tissue. The positive expression rates of RNF6 protein in the Control group, PA group, LST group and CRC group were 40%, 51. 4%, 75. 8% and 91. 4%, respectively, with statistically significant difference between groups (all P<0. 05) . The positive intensity of RNF6 protein in the Control group, PA group, LST group and CRC group showed an increasing trend (P<0. 05) . RNF6 protein expression was associated with the grade of intraepithelial neoplasia in LST patients (P<0. 05), and the positive expression of RNF6 protein in LST tissues with higher intraepithelial neoplasia grade was stronger (Z=-2. 456, P=0. 014) . Conclusion The positive expression rate and positive intensity of RNF6 protein in LST tissues were higher than those in normal adjacent muco‐ sal tissues and PA tissues, and lower than those in colorectal cancer tissues. The higher the grade of intraepithelial neopla‐ sia, the stronger the positive expression of RNF6 protein in LST tissues. [ABSTRACT FROM AUTHOR]

Background: Single-nucleotide polymorphisms (SNPs) in N6-methyladenosine (m6A) related genetic locus play significant roles in tumorigenesis and development. The expression level of many oncogenes and tumour suppressor genes changed because of m6A-associated SNPs. In addition, the relationship between m6A-SNP and bladder cancer (BCa) has not been well studied. Methods: We screened m6A-SNPs in BCa by combining m6A-SNPs data and GWAS-SNPs data. Expression quantitative trait loci (eQTL) and differential expression gene (DEGs) analyses were performed. In ring finger protein, transmembrane 2 (RNFT2), rs3088107 (C > G) was found to have significant eQTL signals and make RNFT2 gene differentially-regulated mostly in BCa. We validated the expression level of RNFT2 in 32 pairs of BCa tissues and eight BCa cell lines by quantitative real-time PCR (qRT-PCR). Functional assays were performed to investigate the role of rs3088107 and RNFT2 in BCa in vitro. Results: We identified 673 m6A-SNPs, which were associated with BCa. Of these m6A-SNPs, 221 showed eQTL signals, amongst which, rs3088107 in RNFT2 showed significant eQTL signals. Results of bioinformatic analyses showed that 11 genes with m6A-SNPs had a differential expression level in BCa. RNFT2 was predicted to be significantly up-regulated in BCa. The qRT-PCR results validated that RNFT2 was highly expressed in our own BCa tissues and cell lines. High expression of RNFT2 also indicated a worse overall survival. We also revealed that rs3088107 (C > G) could inhibit the expression and m6A modification of RNFT2 by qRT-PCR, western-blot and m6A-RIP assays. Moreover, the results of functional assays indicated that RNFT2 promoted BCa cell proliferation and migration. Conclusion: This research found that m6A-SNPs were associated with oncogene RNFT2 in BCa. Furthermore, m6A-SNPs showed great application potential as a new BCa diagnostic biomarker and prognostic indicator. [ABSTRACT FROM AUTHOR]

Mouse double minute 2 homolog (MDM2) is an E3 ubiquitin‐protein ligase that is involved in the transfer of ubiquitin to p53 and other protein substrates. The expression of MDM2 is elevated in cancer cells and inhibitors of MDM2 showed potent anticancer activities. Many inhibitors target the p53 binding domain of MDM2. However, inhibitors such as Inulanolide A and MA242 are found to bind the RING domain of MDM2 to block ubiquitin transfer. In this report, crystal structures of MDM2 RING domain in complex with Inulanolide A and MA242 were solved. These inhibitors primarily bind in a hydrophobic site centered at the sidechain of Tyr489 at the C‐terminus of MDM2 RING domain. The C‐terminus of MDM2 RING domain, especially residue Tyr489, is required for ubiquitin discharge induced by MDM2. The binding of these inhibitors at Tyr489 may interrupt interactions between the MDM2 RING domain and the E2‐Ubiquitin complex to inhibit ubiquitin transfer, regardless of what the substrate is. Our results suggest a new mechanism of inhibition of MDM2 E3 activity for a broad spectrum of substrates. PDB Code(s): 7T59, 7TFG and 7THL; [ABSTRACT FROM AUTHOR]

Ubiquitination and sumoylation are two important posttranslational modifications in cells. RING (Really Interesting New Gene)-type E3 ligases play essential roles in regulating a plethora of biological processes such as cell survival and death. In our previous study, we performed a microarray using inputs from MN9D dopaminergic neuronal cells treated with 6-hydroxydopamine and identified a novel RING-type E3 ligase, RNF166. We showed that RNF166 exerts proapoptotic effects via ubiquitin-dependent degradation of X-linked inhibitor of apoptosis and subsequent overactivation of caspase-dependent neuronal death following 6-hydroxydopamine treatment. In the present study, we further expanded the list of RNF166's binding substrates using mass spectral analyses of immunoprecipitates obtained from RNF166-overexpressing HEK293 cells. Poly (ADP-ribose) polymerase 1, ATPase WRNIP1, X-ray repair cross-complementing protein 5 (Ku80), and replication protein A 70 were identified as potential binding partners of RNF166. Additionally, we confirmed that RNF166 interacts with and forms lysine 63-linked polyubiquitin chains in Ku80. Consequently, these events promoted the increased stability of Ku80. Intriguingly, we found that RNF166 also contains distinct consensus sequences termed SUMO-interacting motifs and interacts with apoptosis signal-regulating kinase 1 (ASK1). We determined that RNF166 induces the sumoylation of ASK1. Overall, our data provide novel evidence that RNF166 has a dual function of Lys63-linked ubiquitination and sumoylation of its cellular targets. [ABSTRACT FROM AUTHOR]

Main conclusion: Molecular function ofRING E3 ligase SbHCI1is involved in ABA-mediated basal heat stress tolerancein sorghum. Global warming generally reduces plant survival, owing to the negative effects of high temperatures on plant development. However, little is known about the role of Really Interesting New Gene (RING) E3 ligase in the heat stress responses of plants. As such, the aim of the present study was to characterize the molecular functions of the Sorghum bicolor ortholog of the Oryza sativa gene for Heat- and Cold-Induced RING finger protein 1 (SbHCI1). Subcellular localization revealed that SbHCI1 was mainly associated with the cytosol and that it moved to the Golgi apparatus under heat stress conditions. The fluorescent signals of SbHCI1 substrate proteins were observed to migrate to the cytoplasm under heat stress conditions. Bimolecular fluorescence complementation (BiFC) and yeast two-hybrid (Y2H) assays revealed that SbHCI1 physically interacted with OsHCI1 ortholog partner proteins in the cytoplasm. Moreover, an in vitro ubiquitination assay revealed that SbHCI1 polyubiquitinated each of the three interacting proteins. The ectopic overexpression of SbHCI1 in Arabidopsis revealed that the protein was capable of inducing abscisic acid (ABA)-hypersensitivity and basal heat stress tolerance. Therefore, SbHCI1 possesses E3 ligase activity and may function as a positive regulator of heat stress responses through the modulation of interacting proteins. [ABSTRACT FROM AUTHOR]

TLR8 (Toll-like receptor 8) is an intracellular pattern recognition receptor that senses RNA in endosomes to initiate innate immune signaling through NF-kB, and mechanisms regulating TLR8 protein abundance are not completely understood. Protein degradation is a cellular process controlling protein concentrations, accomplished largely through ubiquitin transfer directed by E3 ligase proteins to substrates. In the present study, we show that TLR8 has a short halflife in THP-1 monocytes (z1 h) and that TLR8 is ubiquitinated and degraded in the proteasome. Treatment with the TLR8 agonist R848 causes rapid depletion of TLR8 concentrations at early time points, an effect blocked by proteasomal inhibition. We show a novel role for RNF216 (ring finger protein 216), an E3 ligase that targets TLR8 for ubiquitination and degradation. RNF216 overexpression reduces TLR8 concentrations, whereas RNF216 knockdown stabilizes TLR8. We describe a potential role for TLR8 activation by circulating RNA ligands in humans with acute respiratory distress syndrome (ARDS): Plasma and extracted RNA fractions from subjects with ARDS activated TLR8 in vitro. MicroRNA (miRNA) expression profiling revealed several circulating miRNAs from subjects with ARDS. miRNA mimics promoted TLR8 proteasomal degradation in THP-1 cells. These data show that TLR8 proteasomal disposal through RNF216 in response to RNA ligands regulates TLR8 cellular concentrations and may have implications for innate immune signaling. In addition, TLR8 activation by circulating RNA ligands may be a previously underrecognized stimulus contributing to excessive innate immune signaling characteristic of ARDS. [ABSTRACT FROM AUTHOR]

Background Intracranial atherosclerotic stroke is prevalent in Asians. We hypothesized that patients with the ring finger protein 213 (RNF213) variant, a susceptibility locus for moyamoya disease in Asians, have different neuroimaging characteristics in terms of the vessel wall and hemodynamics. Methods and Results We analyzed consecutive patients with ischemic events in middle cerebral artery distribution and relevant plaques of the distal internal carotid artery or proximal middle cerebral artery on high‐resolution magnetic resonance imaging. Patients with carotid/cardiac sources of embolism or moyamoya disease were excluded. High‐resolution magnetic resonance imaging features (eg, outer vessel diameters and plaque characteristics) and fractional flow (as measured by adjusted signal intensity ratio on time‐of‐flight magnetic resonance angiography) were compared between RNF213 p.Arg4810Lys variant carriers and noncarriers. Among 144 patients included, 44 (29.9%) had the RNF213 variant. Clinical characteristics, including age, sex, body mass index, and vascular risk factors, were not significantly different between RNF213 variant carriers and noncarriers. However, the outer vessel diameter was smaller in RNF213 variant carriers than in noncarriers (P

Summary: Recent work has established a core ABA signaling pathway in which A‐type PP2C protein phosphatases act as central negative modulators. Although ABA signaling inhibits PP2C activity through ABA‐receptor complex, it remains unknown if other mechanisms exist to modulate the level of PP2Cs. Here, we identified a RING domain ubiquitin E3 ligase, PIR1 (PP2CA interacting RING finger protein 1), that interacted with PP2CA. Of the two splicing isoforms, PIR1.2 was isolated from leaf tissue. The PIR1.2 exhibited E3 ligase activity and determined PP2CA stability in the presence of ABA. Consistent with the conclusion that PIR1 promotes ABA signaling by removing PP2CA, a negative modulator, the pir1 knockout mutant displayed an ABA‐hyposensitive phenotype. We further showed that PIR2, the closest homologue of PIR1.2, also interacted with PP2CA. Although the pir2 knockout mutant did not display altered ABA response, the pir1‐1/pir2 double mutant became more insensitive to ABA than the wild‐type or pir1‐1 and pir2 single mutants. Using a cell‐free degradation assay, ABA promoted degradation of PP2CA, however, such degradation was delayed when incubated with protein extract prepared from the pir1‐1/pir2 double mutant. Our data suggest that PIR1 and PIR2 positively modulate ABA signaling by targeting PP2CA for degradation. Significance Statement: Several type 2C protein phosphatases (PP2Cs) act as negative modulators of ABA signaling in Arabidopsis. In this study, we isolated the RING‐type E3 ligases PIR1 and PIR2 that interact with and ubiquitinate PP2CA. We revealed that PIR1 and PIR2 play a positive role in ABA signaling via modulation of PP2CA stability. Our findings provide insight into modulation of PP2C in ABA signaling. [ABSTRACT FROM AUTHOR]

Key message: OsHIRP1 is an E3 ligase that acts as a positive regulator in the plant response to heat stress, thus providing important information relating to adaptation and regulation under heat stress in plant. Extreme temperature adversely affects plant growth, development, and productivity. Here, we report the molecular functions of Oryza sativa heat-induced RING finger protein 1 (OsHIRP1), which might play an important role in the response to heat. Transcription of the OsHIRP1 was upregulated in response to heat and drought treatment. We found that the OsHIRP1-EYFP fusion protein was localized to the nucleus after heat treatment (45 °C). Two interacting partners, OsARK4 and OsHRK1, were identified via yeast-two-hybrid screening, which were mainly targeted to the nucleus (OsARK4) and cytosol (OsHRK1), and their interactions with OsHIRP1 were confirmed by biomolecular fluorescence complementation (BiFC). An in vitro ubiquitination assay showed that OsHIRP1 E3 ligase directly ubiquitinates its interacting proteins, OsAKR4 and OsHRK1, as substrates. Using an in vitro cell-free degradation assay, we observed a clear reduction in the levels of the two proteins under high temperature (45 °C), but not under low temperature conditions (4 °C and 30 °C). Seeds of OsHIRP1-overexpressing plants exhibited high germination rates compared with the control under heat stress. The OsHIRP1-overexpressing plants presented high survival rates of approximately 62–68%, whereas control plants displayed a low recovery rate of 34% under condition of acquired thermo-tolerance. Some heat stress-inducible genes (HsfA3, HSP17.3, HSP18.2 and HSP20) were up-regulated in OsHIRP1-overexpressing Arabidopsis than control plants under heat stress conditions. Collectively, these results suggest that OsHIRP1, an E3 ligase, positively regulates plant response to heat stress. [ABSTRACT FROM AUTHOR]

[Display omitted] • A conserved RING finger protein S-R was identified in Schizochytrium. • S-R played a role in biomass accumulation, especially under hypersaline condition. • S-R was involved in the accumulation of TFA and β-carotene. • s-r overexpression raised C14:0 or β-carotene levels by up to 1.78- or 1.61-fold. Strategies for enhancing biomass accumulation and increasing the production of fatty acids and β-carotene in Schizochytrium are hindered by the lack of suitable targets. In this study, S-R, a RING (really interesting new gene) finger domain-containing protein, was identified in Schizochytrium , with homologs found in the family Thraustochytriaceae. Transgenic strains overexpressing S-R showed a minor improvement in cell growth but a significant increase in total fatty acids content by 1.29- to 1.36-fold. Almost all individual saturated fatty acids exhibited significant increases, with the greatest increase observed in the C14:0 content, by 1.52- to 1.78-fold. Additionally, the β-carotene content of S-R strains was significantly upregulated. Overexpression of s - r conferred hypersaline tolerance in Schizochytrium , with a significant increase in dry cell weight, total fatty acids and β-carotene, likely due to the upregulation of glycerol and proline. This study provides a feasible strategy to engineer Thraustochytriaceae for efficient biomass and biochemical production. [ABSTRACT FROM AUTHOR]

Mammalian DNA duplexes are highly condensed with different components, including histones, enabling chromatin formation. Chromatin remodeling is involved in multiple biological processes, including gene transcription regulation and DNA damage repair. Recent research has highlighted the significant involvement of really interesting new gene (RING) finger proteins in chromatin remodeling, primarily attributed to their E3 ubiquitin ligase activities. In this review, we highlight the pivotal role of RING finger proteins in chromatin remodeling and provide an overview of their capacity to ubiquitinate specific histones, modulate ATP-dependent chromatin remodeling complexes and interact with various histone post-translational modifications. We also discuss the diverse biological effects of RING finger protein-mediated chromatin remodeling and explore potential therapeutic strategies for targeting these proteins.

Summary: Abscisic acid (ABA) is a plant hormone that plays a key role in the environmental stress response, especially the induction of ABA‐responsive and stress‐responsive genes and modulation of the stomatal aperture in response to drought stress. Here, we identified CaDILZ1 (CapsicumannuumDrought‐Induced Leucine Zipper 1) belonging to subgroup D of the bZIP protein family; gene functions of this family in response to ABA and drought signaling still remain unknown. CaDILZ1 expression was significantly induced in pepper leaves after exposure to ABA, drought, and NaCl. The CaDILZ1 protein localized in the nucleus of plant cells. In response to drought stress, CaDILZ1‐silenced pepper and CaDILZ1‐overexpressing Arabidopsis plants exhibited drought‐sensitive and drought‐tolerant phenotypes, respectively, via altered ABA content, stomatal closure, and expression of ABA‐responsive and drought‐responsive marker genes. We isolated the RING finger protein CaDSR1 (CapsicumannuumDrought Sensitive RING finger protein 1), which interacted with CaDILZ1 in the nucleus. The CaDSR1 protein exhibited E3 ligase activity and promoted CaDILZ1 degradation via the 26S proteasome pathway. Under drought stress conditions, CaDSR1‐silenced pepper and CaDSR1‐overexpressing Arabidopsis plants exhibited contrasting phenotypes to those of CaDILZ1‐silenced pepper and CaDILZ1‐overexpressing Arabidopsis plants. Taken together, our data suggest that CaDSR1 and CaDILZ1 function in ABA‐mediated drought stress signaling in pepper plants. Significance Statement: The signal transduction occurring in response to drought stress is mediated from transcription to post‐translational modification. Here, the stress‐inducible pepper bZIP protein CaDILZ1 from subgroup D positively regulated ABA‐mediated drought responses, whereas RING‐type E3 ligase CaDSR1 played a contrasting role and triggered ubiquitination and degradation of CaDILZ1; our findings reveal a regulatory mechanism that links CaDILZ1 and CaDSR1 in the drought tolerance and ABA‐mediated responses in pepper plants. [ABSTRACT FROM AUTHOR]

Main conclusion: Our results suggest that a rice E3 ligase, OsMAR1, physically interacts with a cytosolic protein OCPI2 and may play an important role under salinity stress.Salt is an important abiotic stressor that negatively affects plant growth phases and alters development. Herein, we found that a rice gene, OsMAR1 (Oryza sativa microtubule-associated RING finger protein 1), encoding the RING E3 ligase was highly expressed in response to high salinity, water deficit, and ABA treatment. Fluorescence signals of its recombinant proteins were clearly associated with the microtubules in rice protoplasts. Yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) showed that OsMAR1 interacted with a cytosolic protein OCPI2 (O. sativa chymotrypsin protease inhibitor 2) and led to its degradation via the 26S proteasome. Heterogeneous overexpression of OsMAR1 in Arabidopsis showed retarded root growth compared with that of control plants, and then led to hypersensitivity phenotypes under high salinity stress. Taken together, OsMAR1 negatively regulates the salt-stress response via the regulation of the OCPI2 protein in rice. [ABSTRACT FROM AUTHOR]

The accumulation of misfolded proteins in the endoplasmic reticulum (ER) causes ER stress and triggers the unfolded protein response (UPR). Failure to resolve ER stress leads to apoptotic cell death via a yet unclear mechanism. Here, we show that RNF183, a membrane-spanning RING finger protein, localizes to the ER and exhibits classic E3 ligase activities. Sustained ER stress induced by different treatments increases RNF183 protein levels posttranscriptionally in an IRE1α-dependent manner. Activated IRE1 reduces the level of miR-7, which increases the stability of RNF183 transcripts. In addition, overexpression of RNF183 leads to increased apoptosis and its depletion alleviates ER stress-induced apoptosis. Furthermore, RNF183 interacts with Bcl-xL, an antiapoptotic member of the Bcl-2 family, and polyubiquitinates Bcl-xL for degradation. Thus, RNF183 plays an important role in executing programmed cell death upon prolonged ER stress, likely by inducing apoptosis through Bcl-xL. [ABSTRACT FROM AUTHOR]

crucial roles in abiotic stress responses in plants. We report the RING finger E3 ligase gene, an Oryza sativa salt, ABA and drought stress-induced RING finger protein 1 gene (OsSADR1). We demonstrated that although OsSAR1 possesses E3 ligase activity, a single amino acid substitution (OsSADR1C168A) in the RING domain resulted in no E3 ligase activity, suggesting that the activity of most E3s is specified by the RING domain. Additional assays substantiated that OsSADR1 interacts with three substrates-no E3 ligase acti and OsPIRIN, and mediates their proteolysis via the 26S proteasome pathway. For OsSADR1, approximately 62% of the transient signals were in the cytosol and 38% in the nucleus. However, transiently expressed OsSADR1 was primarily expressed in the nucleus (70%) in 200mM salt-treated rice protoplasts. The two nucleus-localized proteins (OsSNAC2 and OsGRAS44) interacted with OsSADR1 in the cytosol and nucleus. Heterogeneous overexpression of OsSADR1 in Arabidopsis resulted in sensitive phenotypes for salt- and mannitol-responsive seed germination and seedling growth. With ABA, OsSADR1 overexpression in plants produced highly tolerant phenotypes, with morphological changes in root length and stomatal closure. The ABA-tolerant transgenic plants also showed hypersensitivity phenotypes under severe water deficit conditions. Taken together, OsSADR1 may act as a regulator in abiotic stress responses by modulating target protein levels. [ABSTRACT FROM AUTHOR]

The retinoic acid-inducible gene-I (RIG-I)-like helicases (RLH)s are cytoplasmic pattern recognition receptors expressed in both immune and non-immune cells that are essential for detection of intracellular RNA products, primarily of viral origin. Upon binding to viral RNA, RLHs interact with mitochondrial antiviral signaling protein (MAVS) to activate interferon (IFN)-mediated antiviral responses. The RLH/MAVS signaling pathway is regulated by ubiquitination/deubiquitination, in which several ubiquitin-editing proteins play critical roles. The really interesting new gene (RING) finger protein 114 (RNF114) was originally identified as a psoriasis susceptibility gene broadly expressed in human tissues. Earlier studies implicated RNF114 in regulating cellular dsRNA responses, cell cycle progression, NF-κB activity and T-cell activation. We found that RNF114 inhibited cellular dsRNA responses and RLH-mediated IFN production. RNF114 functioned as an E3 ubiquitin ligase, and MAVS was identified as a potential target for RNF114-mediated polyubiquitination and degradation. Splenocytes and blood harvested from RNF114 KO showed increased basal IFN level and sensitized responses to dsRNA. However, RNF114 knockout mice failed to exhibit enhance resistance to infection by two acute RNA viruses. These data suggested the potential physiological function of RNF114 in inflammation and host antiviral responses, but demonstrate complexity in the regulation of innate immunity by ubiquitin ligases. [ABSTRACT FROM AUTHOR]

Arenaviruses are a family of enveloped negative-stranded RNA viruses that can cause severe human disease ranging from encephalitis symptoms to fulminant hemorrhagic fever. The bi‑segmented RNA genome encodes four polypeptides: the nucleoprotein NP, the surface glycoprotein GP, the polymerase L, and the RING finger protein Z. Although it is the smallest arenavirus protein with a length of 90 to 99 amino acids and a molecular weight of approx. 11 kDa, the Z protein has multiple functions in the viral life cycle including (i) regulation of viral RNA synthesis, (ii) orchestration of viral assembly and budding, (iii) interaction with host cell proteins, and (iv) interferon antagonism. In this review, we summarize our current understanding of the structural and functional role of the Z protein in the arenavirus replication cycle.

Ubiquitination plays a very important role in the response to abiotic stresses of plant. To identify key regulators of salt stress, a gene GhSARP1 (Salt-Associated Ring finger Protein)encoding C3H2C3-type E3 ligase, was cloned from cotton. Transcription level of GhSARP1 was high in leaf, flower and fiber of 24,27 and 27DPA (Days Post-Anthesis), but low in root and stem. Except PEG6000 treatment, the expression of GhSARP1 was down-regulated by NaCl, cold and ABA after being treated for 1 h. GhSARP1-GFP fusion protein located on the plasma membrane, which was dependent on trans -membrane motif. In vitro ubiquitination assay showed that GhSARP1 had E3 ligase activity. Heterogeneous overexpression of GhSARP1 reduced salt tolerance of transgenic Arabidopsis in germination and post-germination stage. Our results suggested that the GhSARP1 might negatively regulate the response to salt stress mediated by the ubiquitination in cotton. [ABSTRACT FROM AUTHOR]

Many reports indicate that RING finger proteins play key roles in regulating plant defense responses against abiotic and biotic stresses, but few have thus far been investigated in economic fruit, such as bananas. In this study, a RING finger gene, designated MaRING1 , was isolated and characterized from banana fruit. MaRING1 belonged to the ATL RING-H2 finger protein family, and localized preferentially to the nucleus. Gene expression profiles revealed that MaRING1 was cold-responsive and induced by methyl jasmonate (MeJA) treatment during cold storage. Moreover, yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays showed that MaRING1 physically interacted with MaMYC2a, a transcription factor (TF) related to MeJA-induced chilling tolerance of banana fruit. Taken together, our results suggest that MaRING1 might functionally coordinate with MaMYC2a in response to cold stress of banana fruit, expanding our understanding of the possible involvement of RING finger proteins in the regulatory network of MeJA-induced chilling tolerance. [ABSTRACT FROM AUTHOR]