Ask about this productRelated genes to: ZCCHC14 antibody
- Gene:
- ZCCHC14 NIH gene
- Name:
- zinc finger CCHC-type containing 14
- Previous symbol:
- -
- Synonyms:
- BDG29, MGC14139
- Chromosome:
- 16q24.2
- Locus Type:
- gene with protein product
- Date approved:
- 2004-07-14
- Date modifiied:
- 2016-02-12
Related products to: ZCCHC14 antibody
Related articles to: ZCCHC14 antibody
- Both hepatitis B virus (HBV), an hepadnavirus with a DNA genome, and hepatitis A virus (HAV), a picornavirus, require the TRAMP-like host ZCCHC14-TENT4 complex for efficient replication. However, whereas HBV requires the nucleotidyltransferase activity of TENT4 to extend and stabilize the 3' poly(A) tails of mRNA transcribed from its genome, the role played by TENT4 in HAV replication is uncertain. HAV proteins are synthesized directly from its genomic RNA, which possesses a 3' poly(A) tail, with its length and composition presumably maintained by 3D-catalyzed RNA transcription during its replicative cycle. Using nanopore long-read sequencing of RNA from infected cells, we confirm here that the length of the HAV 3' poly(A) tail is not altered by treating infected cells with RG7834, a small molecule TENT4 inhibitor with potent anti-HAV activity. Despite this, TENT4 catalytic activity is essential for HAV replication. Surprisingly, nanopore sequencing revealed a low abundance of HAV subgenomic RNAs (hsRNAs) that extend from the 5' end of the genome to a site within the 5' untranslated RNA (5'UTR) immediately downstream of a stem-loop to which the ZCCHC14-TENT4 complex is recruited. These hsRNAs are polyadenylated, and their abundance is sharply reduced by RG7834 treatment, implying they are likely products of TENT4. Similar subgenomic RNAs were not identified in poliovirus-infected cells. hsRNAs are present not only in HAV-infected cell culture but also in the liver of HAV-infected mice, where they represent 1-3% of all HAV transcripts, suggesting their physiological relevance. However, transfecting exogenous hsRNA into TENT4-depleted cells failed to rescue HAV replication, leaving the functional role of hsRNA unresolved. These findings reveal a novel picornaviral subgenomic RNA species while highlighting mechanistic differences in the manner in which HAV and HBV exploit the host ZCCHC4-TENT4 complex for their replication. - Source: PubMed
Publication date: 2025/05/02
Li YouGupta AnkitPapas Brian NAponte-Diaz DavidHarris Jayden MMisumi IchiroWhitmire Jason KCameron Craig EMorgan MarcosLemon Stanley M - SAG-524 is a novel, oral HBV RNA destabilizer developed to address the limitations of treatment with nucleos(t)ide analogues (NAs), which are effective against HBV DNA but show limited efficacy in reducing hepatitis B surface antigen (HBsAg) levels. SAG-524 exerts its effect by destabilizing HBV RNA by shortening the poly(A) tail, which leads to a significant reduction of both pgRNA and PreS/S mRNA. This destabilization seems to be specific for HBV RNA molecules. The mechanism involves the recruitment of PAPD5/7 by ZCCHC14 to the HBV RNA, where guanine is incorporated into the poly(A) tail to protect against degradation. SAG-524 disrupts this process by directly targeting PAPD5, thus destabilizing HBV RNA. In preclinical trials, oral administration of SAG-524 reduced serum HBsAg levels in HBV-infected PXB mice. When combined with NAs or capsid assembly modulators (CAMs), significant reductions in HBsAg, HBV DNA, and intrahepatic covalently closed circular DNA were observed. Safety studies conducted over 13 weeks in mice and monkeys revealed no significant toxicity, demonstrating the drug demonstrated a favorable safety profile. In conclusion, the novel mechanism of action, high oral bioavailability, and strong suppression of HBsAg make SAG-524 a promising candidate for future therapeutic use. The potential for combination therapy with NAs or CAMs underscores its capacity to contribute to achieving a functional cure for chronic HBV infection. - Source: PubMed
Tanaka Yasuhito - Individuals with Down syndrome exhibit a higher prevalence of periodontal disease, which can lead to implant loss. This study aims to identify genetic markers associated with implant loss in these patients, providing insight into potential predictive and therapeutic approaches. A systematic analysis was conducted, including both clinical and genetic data from Down syndrome patients with a history of dental implants. Genetic profiling was performed using Transcriptome Analysis Console (TAC version 4.0 Applied Biosystems, Thermo Fisher Scientific, Waltham, MA, USA), focusing on genes previously implicated in periodontal disease and bone metabolism. Statistical analysis identified correlations between genetic variants and implant survival rates. The analysis revealed statistically significant alterations in several genes related to inflammation and bone remodeling. Key findings included alterations in the expression of the genes , , , , , and in patients with implant failure. These genetic markers were strongly correlated with compromised osseointegration and implant loss. These findings underline the role of genetic predisposition in the failure of dental implants among individuals with Down syndrome. Genetic markers, particularly those involved in inflammation and bone metabolism, play a critical role in implant loss among Down syndrome patients with periodontal disease. Recognizing these markers can aid in early diagnosis and personalized treatment strategies, potentially improving implant success rates. - Source: PubMed
Publication date: 2025/01/22
Cortés-Eslava DanielaGómez-Díaz RaquelTorres-Lagares DanielMachuca-Portillo GuillermoGutiérrez-Pérez José-LuisSerrera-Figallo María-ÁngelesBaus-Domínguez María - Expression of microRNAs, such as miR-365, is known to be dysregulated in many tumors, including oral cancers, although little is known about their role or functions. The objective of this project is to evaluate the downstream targets of miR-365 to determine any potential pathways or effects. Downstream targets for miR-365 (miRdatabase target scores > 90) were used for qPCR screening of oral cancer cell lines (SCC4, SCC9, SCC15, SCC25, CAL27). Each oral cancer cell line expressed miR-365 downstream targets molybdenum cofactor synthesis-2 (MOCS2), erythropoietin receptor (EPOR), IQ motif containing-K (IQCK), carboxypeptidase A3 (CPA3), solute carrier family 24 member-3 (SLC24A3), and coiled-coil domain containing 47 (CCDC47)-although the expression levels varied somewhat. However, differential results were observed with ubiquitin protein ligase E3 component n-recognin-3 (UBR3), nudix hydrolase-12 (NUDT12), zinc finger CCHC-type containing-14 (ZCCHC14), and homeobox and leucine zipper encoding (HOMEZ). These data suggest that many of the miR-365 targets are expressed in the oral cancers screened, with the differential expression of UBR3, ZCCHC14, HOMEZ, and NUDT12, which may be correlated with chemoresistance among two specific oral cancer cell lines (SCC25, SCC9). These results suggest this differential expression may signal potential targets for patient treatment with tumors exhibiting miR-365 and chemotherapeutic resistance. - Source: PubMed
Publication date: 2024/06/10
Yu BrendonKruse NathanielHoward Katherine MKingsley Karl - The post-transcriptional regulatory element (PRE) is present in all HBV mRNAs and plays a major role in their stability, nuclear export, and enhancement of viral gene expression. Understanding PRE's structure, function, and mode of action is essential to leverage its potential as a therapeutic target. A wide range of PRE-based reagents and tools have been developed and assessed in preclinical and clinical settings for therapeutic and biotechnology applications. This manuscript aims to provide a systematic review of the characteristics and mechanism of action of PRE, as well as elucidating its current applications in basic and clinical research. Finally, we discuss the promising opportunities that PRE may provide to antiviral development, viral biology, and potentially beyond. - Source: PubMed
Publication date: 2024/03/29
Mouzannar KarimSchauer AnneLiang T Jake