POLS Blocking Peptide
- Known as:
- POLS Blocking Peptide
- Catalog number:
- 33r-9878
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- Fitzgerald industries international
- Gene target:
- POLS Blocking Peptide
Related genes to: POLS Blocking Peptide
- Gene:
- TENT4A NIH gene
- Name:
- terminal nucleotidyltransferase 4A
- Previous symbol:
- POLS, PAPD7
- Synonyms:
- POLK, TRF4, LAK-1, TRF4-1
- Chromosome:
- 5p15.31
- Locus Type:
- gene with protein product
- Date approved:
- 2001-09-27
- Date modifiied:
- 2018-04-20
Related products to: POLS Blocking Peptide
Related articles to: POLS Blocking Peptide
- Numerous studies have identified a large number of miRNA editing sites via deep sRNA sequencing profiling of tissue samples. However, the single-cell landscape of miRNA editing patterns has remained largely unknown to date. To investigate miRNA editing and mutation characteristics at single cell level, this study analyzed miRNA editing and mutation events in 448 single-cell small RNA sequencing profiles from 5 different cell types. Our results revealed that PCA and clustering analysis, performed based on the editing levels of identified miRNA editing sites, could distinguish distinct cell types, indicating that miRNA editing patterns are cell-type-specific across different cellular populations. We further demonstrated that a subset of miRNA editing sites exhibited strict cell-type-specific editing patterns. Meanwhile, within the same cell type, the identified sites presented different distributions of editing levels in different cells. A fraction of sites showed highly variable editing levels among different cells of the same cell type, while some sites displayed relatively uniform and consistent editing patterns. An A-to-I editing site in hsa-mir-376c, i.e., hsa-mir-376c 48 A g, showed a significantly higher editing level in glioblastoma cells than in naive embryonic stem cells, suggesting a potential role in the initiation and progression of glioblastoma. Furthermore, our results also suggest that in leukemia cells, TENT4A, TENT5A, TENT5B, TENT5C, TENT5D, and TUT1 may mediate the non-templated nucleotide additions to the 3'ends of miRNAs. - Source: PubMed
Publication date: 2026/04/09
Mao ChunyiGuo HaoXie WenpingXu YueZhang HongjiaLuo KangYang JunZheng Yun - Small noncoding RNAs (sncRNAs) are subject to 3'-end trimming and tailing activities that impact maturation versus degradation decisions during biogenesis. To investigate the dynamics of human sncRNA 3'-end processing at a global level, we performed genome-wide 3'-end sequencing of newly transcribed and steady-state sncRNAs. This revealed widespread post-transcriptional adenylation of newly transcribed sncRNAs, which came in two distinct varieties. One is characterized by oligoadenylation, which is transient, promoted by TENT4A/4B polymerases, and most commonly observed on unstable small nucleolar RNAs that are not fully processed at their 3'-ends. The other is characterized by monoadenylation, which is broadly catalyzed by TENT2 and, in contrast to oligoadenylation, stably accumulates at the 3'-end of sncRNAs, including Polymerase-III-transcribed (Pol-III) RNAs and a subset of small nuclear RNAs. Monoadenylation inhibits Pol-III RNA post-transcriptional 3'-uridine trimming and extension and, in the case of 7SL RNAs, prevents their accumulation with nuclear La protein and promotes their biogenesis towards assembly into cytoplasmic signal recognition particles. Thus, the biogenesis of human sncRNAs involves widespread mono- or oligoadenylation with divergent impacts on sncRNA fates. - Source: PubMed
Publication date: 2025/12/05
Ocheltree CodySkrable BlakePimentel AnastasiaNicholson-Shaw TimothyLee Suzanne RLykke-Andersen Jens - Poly(A) RNA polymerases D5 and D7 (PAPD5, PAPD7) are host factors that stabilize hepatitis B virus (HBV) RNA transcripts. RO7239958, a liver-targeted locked nucleic acid (LNA) antisense oligonucleotide (ASO), induces intracellular degradation of PAPD5- and PAPD7-encoding messenger RNAs (mRNAs). This first-in-human study evaluated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of RO7239958 in healthy volunteers and adults with chronic hepatitis B (CHB) receiving standard-of-care antiviral therapy. Forty healthy volunteers were randomized (4:1) to single ascending subcutaneous doses of RO7239958 (0.1, 0.3, 1.0, or 1.5 mg/kg) or placebo. Based on a population PK model built to predict liver exposure, two parallel CHB cohorts ( = 8 and = 7 per cohort) were randomized to two 4-weekly doses of RO7239958 (0.2 or 0.4 mg/kg) or placebo. RO7239958 plasma exposure increased more than dose-proportionally at dose levels of 1.0 and 1.5 mg/kg, suggesting saturation of liver uptake. RO7239958 was generally well tolerated in healthy volunteers; transaminase elevations occurred at the highest doses, including one reversible Grade 3 elevation. The PK model indicated that doses of 0.2 and 0.4 mg/kg would reduce PAPD5 and PAPD7 mRNA by 50% and 62%, respectively, with minimal liver toxicity. Consistent with predictions, RO7239958 was well-tolerated and safe in patients. At 0.4 mg/kg, the maximum reduction from baseline in serum hepatitis B surface antigen was observed on Day 43 (mean decline 0.2 log IU/mL; range 0.0-0.5 log IU/mL). While RO7239958 showed a potentially narrow therapeutic window, PAPD5 and PAPD7 remain potential therapeutic targets in HBV curative strategies.CLINICAL TRIALSThis study was registered at NCT03762681. - Source: PubMed
Publication date: 2025/11/04
Geretti Anna MariaSostelly AlexandreBuatois SimonLu SijieLemenuel AnnabelleAttley GemmaBopst MartinAlvarez-Sánchez RubénMueller HenrikGane Edward - 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 - Despite the considerable clinical and economic burden imposed by hepatitis A virus (HAV) infection, both globally and in U.S., there are currently no available antiviral therapies for the treatment of type A hepatitis. Here we describe novel third-generation hepato-selective dihydroquinolizinones (HS-DHQs) with cellular uptake mediated by transport via hepatocyte-specific solute organic anion transporter family members 1B1 and 1B3 (OATP1B1-B3). The lead HS-DHQ compound, HS83128, demonstrates robust inhibition of the host cell TENT4A/B terminal nucleotidyltransferases required for efficient HAV RNA synthesis (IC 6-25nM), and potent antiviral activity against HAV in cell culture (EC 0.6 nM). Pharmacokinetic studies in CD-1 mice receiving comparable oral doses of HS83128 and a first-generation dihydroquinolizinone, RG7834, revealed a 5-fold increase in intrahepatic drug concentration and more than 10-fold improvement in liver versus nervous system tissue selectivity. Twice-daily oral administration of HS83128 rapidly arrested viral replication in HAV-infected Ifnar1 mice, reducing fecal virus shedding and cytokine markers of hepatic inflammation and reversing virus-induced liver injury. The hepato-selective nature of HS83128 may reduce the risk of neurologic and reproductive track toxicities observed with long-term administration of other dihydroquinolizinones, making it a candidate for the first antiviral therapy of hepatitis A. - Source: PubMed
Publication date: 2025/03/19
Misumi IchiroYue ZhizhouJiang ZhengyuanKarampoori AnilkumarWhitmire Jason KCullen John MBlock TimothyLemon Stanley MDu YanmingLi You