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CircMAP2 attenuates synaptic impairment in neurons subjected to cerebral ischaemia/reperfusion injury.

BACKGROUND: Acute ischaemic stroke (AIS) is a major cause of disability and mortality worldwide, yet rapid diagnostic tools and effective ne … nscriptional assays to evaluate interactions with U1 small nuclear ribonucleoprotein (U1 snRNP) and RNA polymerase II. RESULTS: CircMAP2 was significantly upregulated in the peri-infarct and ischaemic core of middle cerebral artery occlusion/reperfusion mice, as well as in AIS patient plasma. Regression analysis linked elevated CircMAP2 levels to larger infarct vo …

Nonnucleoside inhibitors of norovirus RNA polymerase: scaffolds for rational drug design.

Norovirus (NoV) is the leading cause of acute gastroenteritis worldwide, causing over 200,000 deaths a year. NoV is nonenveloped, with a single-stranded RNA genome, and is primarily transmitted person to person. The viral RNA-dependent RNA polymerase (RdRp) is critical for the production of genomic and subgenomic RNA and is therefore a prime target for antiviral therapies. Using high-throughput screening, nearly 20,000 "lead-like" compounds were tested for inhibitory activity against the NoV genogroup II, genotype 4 (GII.4) RdRp. The four most potent hits demonstrated half-maximal inhibitory c

Integrated deep learning and multi-scale modeling for the discovery of pan-genotypic HCV NS5B polymerase inhibitors.

Chronic Hepatitis C Virus (HCV) infection remains a significant global health challenge, necessitating the development of pan-genotypic inhibitors to overcome the limitations of genotype-specific therapies. The NS5B RNA-dependent RNA polymerase, particularly its conserved Palm II region, is a promising target for such broad-spectrum antivirals. In this study, we integrated advanced deep learning and multi-scale computational approaches to design novel pan-genotypic HCV NS5B inhibitors. First, we employed AlphaFold3 to predict the high-resolution structures of NS5B polymerase from genotypes wit

Resveratrol Inhibits Abdominal Aortic Aneurysm Progression by Reducing Extracellular Matrix Degradation, Apoptosis, Autophagy, and Inflammation of Vascular Smooth Muscle Cells via Upregulation of HMOX1.

OBJECTIVE: This study aimed to explore the therapeutic effect of resveratrol (RES) against abdominal aortic aneurysm (AAA) and the role of HMOX1 underlying this effect. METHODS: Vascular smooth muscle cells (VSMCs) were induced by angiotensin II (Ang II) to construct the microenvironment of AAA. HMOX1 expression was downregulated by the short hairpin ribonucleic acid (RNA) specific to HMOX1 in RES-pretreated VSMCs. The levels of matrix metalloproteinase (MMP)-2, MMP-9, and elastin were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot. Apoptos

Organization and Dynamics of Transcription Elongation Foci in Mouse Tissues.

RNA polymerase II (RNAP2) transcribes most genes in eukaryotic nuclei. During the transition from transcription initiation to productive elongation, and throughout the elongation phase, RNAP2 becomes phosphorylated at the Ser2 residue within the heptapeptide repeats of the carboxyl-terminal domain of its largest subunit. Antibodies specific to RNAP2 Ser2 phosphorylation (Ser2ph) have enabled visualization of active transcription sites in fixed cells and tissues. Here, we report the generation and characterization of knock-in mice ubiquitously expressing a fluorescent protein-tagged, modificati…

Discovery of novel CDK9 inhibitors containing 1H-pyrrolo[2,3-b]pyridine moiety for treatment of colorectal cancer.

In this work, YK-2168 was selected as the lead compound for the development of a series of highly selective CDK9 inhibitors due to its unique 1H-pyrrolo[2,3-b]pyridine scaffold, which acts as an optimal backbone for targeting the kinase hinge region. The optimized compound B3 exhibited potent inhibitory activities at both enzymatic and cellular levels with satisfactory selectivity. Mechanistic studies revealed that compound B3 induces apoptosis in the HCT116 cells by suppressing the phosphorylation of RNA polymerase II at Ser2 site, which further results in the downregulates the expression of …

Chromatin profiling for everyone: FFPE-CUTAC for the theory and practice of modern molecular biology.

In 2025, together with the Fred Hutch Summer Undergraduate Research and Summer High School Internship programs, we developed and implemented a laboratory genomics research experience to introduce students to modern molecular biology techniques and bioinformatics. The course centered around using a new method we had developed in 2023 that uses readily available fixed tissue sections on glass slides. Students performed a series of steps to tagment genomic locations of RNA Polymerase II and then used PCR to enrich libraries for next-generation sequencing in a core facility. Students then visualiz…

Nuclear Wave1 is required for reprogramming transcription in oocytes and for normal development.

Eggs and oocytes have a remarkable ability to induce transcription of sperm after normal fertilization and in somatic nuclei after somatic c … by its WHD domain to active transcription components, and this binding contributes to the action of RNA polymerase II. We identify Wave1 as a maternal reprogramming factor that also has a necessary role in gene activation in development.

Неизъятие транскрипции хостовых клеток полиомиелитвирусом: разрыв коэффициента транскрипции CREB по полиомиелитвирусно кодированному протезе 3Cpro.

Принимающая клетка PNA полимераза II средоточивается полиомиелитвирусной инфекцией. Предыдущие исследования нашей лаборатории показали, что активированная транскрипция с помощью циклического элемента, содержащего AMP (CRE)-содержащего в себе элемент, была сильно ограничена в экстрактах, полученных из клеток, инфицированных полиомиелитом, по сравнению с клетками из имитационных клеток. Здесь мы показываем, что связывающий CRE белок, CREB, конкретно изливается полиомиелитвирусной протезией 3Cpro как in vitro, так и в инфицированных вирусом клетках. Протеолитический разрыв CREB приводит к значите

Совпадение в аннотации оригинала
Host cell RNA polymerase II-mediated transcription is inhibited by poliovirus infection. Previous studies from our laboratory showed that activated transcription from a cyclic AMP-responsive element (CRE)-containing promoter was severely inhibited in extracts prepared from poliovirus-infected HeLa cells compared to those from mock-infected cells. Here we dem…

Cleavage of transcriptional activator Oct-1 by poliovirus encoded protease 3Cpro.

In HeLa cells, RNA polymerase II mediated transcription is severely inhibited by poliovirus infection. Both basal and activated transcription are affected to bring about a complete shutoff of host cell transcription. We demonstrate here that the octamer binding transcription factor, Oct-1, is cleaved in HeLa cells infected with poliovirus. Incubation of Oct-1 with the purified, recombinant 3Cpro results in the generation of the cleaved Oct-1 product seen in virus infected cells. Poliovirus infection leads to the formation of altered Oct-1 DNA complexes that can also be generated by incubation …

Molecular insights into type I interferon suppression and enhanced pathogenicity by species B human adenoviruses B7 and B14.

Human adenoviruses (HAdVs) are small DNA viruses that generally cause mild disease. Certain strains, particularly those belonging to species … on of interferon-stimulated gene expression. Unlike in HAdV-C2, HAdV-B7 and B14 sequester STAT2 and RNA polymerase II from interferon-stimulated gene promoters in infected cells. This results in suppressed interferon- stimulated gene activation. In addition, we show that RuvBL1 and RuvBL2, cofactors important for RNA polymerase II recruitment to promoters and inter …

Phylogenetic depth of the bacterial genera Aquifex and Thermotoga inferred from analysis of ribosomal protein, elongation factor, and RNA polymerase subunit sequences.

The phylogenetic placement of the Aquifex and Thermotoga lineages has been inferred from (i) the concatenated ribosomal proteins S10, L3, L4, L23, L2, S19, L22, and S3 encoded in the S10 operon (833 aa positions); (ii) the joint sequences of the elongation factors Tu(1alpha) and G(2) coded by the str operon tuf and fus genes (733 aa positions); and (iii) the joint RNA polymerase beta- and beta'-type subunits encoded in the rpoBC operon (1130 aa positions). Phylogenies of r-protein and EF sequences support with moderate (r-proteins) to high statistical confidence (EFs) the placement of the two

SHP-1 dephosphorylates histone H2B to facilitate its ubiquitination during transcription.

Dynamic regulation of phosphorylation and dephosphorylation of histones is essential for eukaryotic transcription, but the enzymes engaged i … Y121, leads to a reduction in genome-wide H2B ubiquitination, which subsequently causes defects in RNA polymerase II-dependent transcription. Mechanistically, we demonstrate that Y121 phosphorylation precludes H2B's interaction with the E2 enzyme, indicating that SHP-1-mediated dephosphorylation of this residue may be a prerequisite for efficient H2B ubiquitinatio …

RNA Sequencing of Primary Cutaneous and Breast-Implant Associated Anaplastic Large Cell Lymphomas Reveals Infrequent Fusion Transcripts and Upregulation of PI3K/AKT Signaling via Neurotrophin Pathway Genes.

Cutaneous and breast implant-associated anaplastic large-cell lymphomas (cALCLs and BI-ALCLs) are two localized forms of peripheral T-cell l … more conspicuous in BI-ALCL, as well as differences, i.e., over-expression of genes involved in the RNA polymerase II transcription program in BI-ALCL and of the RNA splicing/processing program in cALCL.

AFF4, a component of the ELL/P-TEFb elongation complex and a shared subunit of MLL chimeras, can link transcription elongation to leukemia.

Chromosomal translocations involving the MLL gene are associated with infant acute lymphoblastic and mixed lineage leukemia. There are a lar … 4, and several other factors. AFF4 is required for SEC stability and proper transcription by poised RNA polymerase II in metazoans. Knockdown of AFF4 in leukemic cells shows reduction in MLL chimera target gene expression, suggesting that AFF4/SEC could be a key regulator in the pathogenesis of leukemia through many of the MLL partners.

Mechanism of promoter melting by the xeroderma pigmentosum complementation group B helicase of transcription factor IIH revealed by protein-DNA photo-cross-linking.

The p89/xeroderma pigmentosum complementation group B (XPB) ATPase-helicase of transcription factor IIH (TFIIH) is essential for promoter melting prior to transcription initiation by RNA polymerase II (RNAPII). By studying the topological organization of the initiation complex using site-specific protein-DNA photo-cross-linking, we have shown that p89/XPB makes promoter contacts both upstream and downstream of the initiation site. The upstream contact, which is in the region where promoter melting occurs (positions -9 to +2), requires tight DNA wrapping around RNAPII. The addition of hydrolyza…

Inhibitory action of phospholipid-interacting drugs on transcription initiation in a nuclear extract of Ehrlich ascites tumor cells.

Drugs with affinity for phospholipids, such as chlorpromazine, verapamil, tetracaine and imipramine, were found to inhibit accurate transcri … ion at the step of initiation, not elongation. Moreover, it did not affect the activity of purified RNA polymerase II, suggesting the interaction of phospholipids with transcription factors in the nuclear extract. Some transcription factors in the nuclear extract were found to have affinity for cardiolipin, and were precipitated with excess cardiolipin. The transcr …

Hepatitis B virus subtypes and hepatitis C virus genotypes in patients with chronic liver disease in Nepal.

A total of 145 patients with chronic liver disease, including 20 with chronic hepatitis, 63 with cirrhosis and 62 with primary hepatocellular carcinoma from Nepal were tested for markers of hepatitis B virus or hepatitis C virus infection. HBsAg was detected in 57 (39%) and hepatitis C virus RNA in 12 (8%); the cause of liver disease was not known in the remaining 76 (52%). HBsAg was found in 5 (1.3%) of 379 normal controls, whereas hepatitis C virus-associated antibodies were detected in 13 (3.4%), none of whom was positive for serum hepatitis C virus RNA. Subtypes of 102 HBsAg samples, from

CDK9 inhibition blocks the initiation of PINK1-PRKN-mediated mitophagy by regulating the SIRT1-FOXO3-BNIP3 axis and enhances the therapeutic effects involving mitochondrial dysfunction in hepatocellular carcinoma.

Mitophagy is a type of selective macroautophagy/autophagy that degrades dysfunctional or excessive mitochondria. Regulation of this process … ; PB: phosphate buffer; PDX: patient-derived tumor xenograft; PINK1: PTEN induced kinase 1; POLR2A: RNA polymerase II subunit A; p-POLR2A-S2: Ser2 phosphorylation of RNA polymerase II subunit A; PRKN: parkin RBR E3 ubiquitin protein ligase; SIRT1: sirtuin 1.

DDX21 Promotes Breast Cancer Growth and Metastasis via Stimulating RNAPII Elongation During Hypoxia.

Hypoxia is a hallmark of solid tumors, and hypoxia-inducible factors (HIFs) are the master transcription factors that allow cancer cells to … ates the transcription elongation of HIF target genes by elevating the enrichment of phosphorylated RNA Polymerase II at serine 2 on the hypoxia-response element of HIF target genes. These target genes, including IGFBP1, WNT1, WNT10B, TGFB1, PCK1, and SLC2A3, are critical for cancer cell proliferation and metastasis. Consequently, DDX21 enhances breast cancer cell …