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Last update 23 Jan 2025

RNGTT

Last update 23 Jan 2025

Basic Info

Synonyms

CAP1A, GTase, GTP--RNA guanylyltransferase

+ [10]

Introduction

Bifunctional mRNA-capping enzyme exhibiting RNA 5'-triphosphate monophosphatase activity in the N-terminal part and mRNA guanylyltransferase activity in the C-terminal part. Catalyzes the first two steps of cap formation: by removing the gamma-phosphate from the 5'-triphosphate end of nascent mRNA to yield a diphosphate end, and by transferring the GMP moiety of GTP to the 5'-diphosphate terminus of RNA via a covalent enzyme-GMP reaction intermediate.

Drugs associated with RNGTT

Peginterferon alfa-2a/Ribavirin

Target

IFNAR x IMPDH x RNAP x RNGTT

Mechanism

IFNAR agonists [+5]

Active Org.

Hoffmann-La Roche, Inc.

Originator Org.

Hoffmann-La Roche, Inc.

Active Indication

Hepatitis C, Chronic

Inactive Indication-

Drug Highest PhaseApproved

First Approval Ctry. / Loc.

First Approval Date04 Jun 2004

Peginterferon alfa-2b/Ribavirin(Merck & Co., Inc.)

Target

IFNAR x IMPDH x RNAP x RNGTT

Mechanism

IFNAR agonists [+5]

Active Org.

Schering Corp.

Originator Org.

Merck & Co., Inc.

Active Indication

Hepatitis C

Inactive Indication

Chronic hepatitis C genotype 1 [+2]

Drug Highest PhaseApproved

First Approval Ctry. / Loc.

First Approval Date13 Aug 2002

Interferon alfa-2b/Ribavirin

Target

IFNAR x IMPDH x RNAP x RNGTT

Mechanism

IFNAR agonists [+5]

Active Org.

Schering-Plough Corp.

Originator Org.

Merck Sharp & Dohme Corp.

Active Indication

Hepatitis C

Inactive Indication-

Drug Highest PhaseApproved

First Approval Ctry. / Loc.

First Approval Date14 Jun 1998

992

Clinical Trials associated with RNGTT

NCT06744777

/ RecruitingPhase 3IIT

The Comparative Efficacy of Standard Treatment Plus Ribavirin vs Standard Treatment Alone in Preventing Clinically Significant Hemorrhage in Patients With Dengue Fever: A Double-blind, Randomized Control Trial

This study investigates the comparative efficacy of standard treatment plus Ribavirin versus standard treatment alone in preventing clinically significant hemorrhage among patients diagnosed with dengue fever. It is a double-blind, randomized control trial aimed at determining whether the addition of Ribavirin improves clinical outcomes, particularly reducing bleeding events.

Start Date17 Dec 2024

Sponsor / Collaborator

Khyber Medical University

ChiCTR2400088070

/ SuspendedNot ApplicableIIT

Efficacy and safety of peginterferon a in the treatment of patients with advanced liver fibrosis and chronic hepatitis B

Start Date10 Aug 2024

Sponsor / Collaborator

Affiliated Hospital of Xuzhou Medical University

NCT06488300

/ Not yet recruitingPhase 2IIT

Assessment of Respiratory SYNcytial Virus antivirALs: A Phase 2 Multi-centre Adaptive Randomised Platform Trial For the Assessment of Antiviral Pharmacodynamics in aCute Symptomatic RSV Infection (ARSYNAL-FC)

This trial will use a previously validated platform, to quantitatively assess antiviral effects in low-risk patients with high viral burdens and uncomplicated Respiratory Syncytial Virus (RSV), to determine in-vivo antiviral activity. In this randomised, open-label, controlled, group sequential adaptive platform trial, we will assess and compare the performance of currently licensed interventions (including repurposed drugs) with activity against RSV, and those with potential activity demonstrated in pre-clinical and early clinical studies relative to each-other, and the control (no antiviral treatment).
ARSYNAL-FC study is funded by Wellcome Trust Grant ref: 226933/Z/23/Z through the COVID-19 Therapeutics Accelerator

Start Date01 Jul 2024

Sponsor / Collaborator

University of Oxford

100 Clinical Results associated with RNGTT

100 Translational Medicine associated with RNGTT

0 Patents (Medical) associated with RNGTT

290

Literatures (Medical) associated with RNGTT

19 Nov 2024·Analytical Chemistry

Novel Ratiometric Surface-Enhanced Raman Scattering (SERS) Biosensor for Ultrasensitive Quantitative Monitoring of Human Carboxylesterase-1 in Hepatocellular Carcinoma Cells Using Ag–Au Nanoflowers as SERS Substrate

Article

Author: Feng, Jun ; Wang, Ying ; Chen, Qiying ; Huang, Wenyi ; Dong, Wuheng ; Gao, Si ; Li, Lijun ; Cheng, Hao ; Zhan, Yaqin ; Chen, Ruijue ; Zhou, Pei

In this study, we developed ratiometric surface-enhanced Raman scattering (SERS) biosensors using Ag-Au alloy nanoflowers as SERS substrates, molecules having amide bonds and alkyne groups (Tag A) as Raman reporters, and sodium thiocyanate as an internal standard molecule (Tag B) for the sensitive detection of human carboxylesterase-1 (hCE1) in HepG-2 cells. The correlation between HepG-2 cell damage and hCE1 activity levels was investigated. Both Tag A's alkyne group and Tag B's cyanide group produced characteristic SERS signals in the Raman-silent region (I_2000 cm^-1 and I_2115 cm^-1, respectively). The hydrolysis of the amide bond in Tag A via hCE1 and the shedding of the alkyne group led to a reduction in the SERS signal intensity observed at I_2000 cm^-1. Conversely, the SERS signal intensity of Tag B at I_2115 cm^-1 exhibited a consistent pattern. As the activity level of hCE1 and the ratiometric peak intensity (I_2000 cm^-1/I_2115 cm^-1) correlated negatively, hCE1 could be quantitatively detected within the range of 10^-2 to 2 × 10² ng·mL^-1, with a detection limit of 7.3 pg·mL^-1. The ratiometric SERS probe strategy, in which a ratio response is employed, permits sensitive and reproducible SERS detection by facilitating intrinsic calibration to rectify signal fluctuations resulting from temporal and spatial variations in the detection conditions. Concurrently, the implementation of Raman-silent region reporter molecules mitigates the interference from endogenous biomolecules in SERS measurements and offers a novel approach for achieving highly sensitive and interference-free detection of intracellular hCE1.

01 Jun 2024·Journal of Cell Science

The mRNA-capping enzyme localizes to stress granules in the cytoplasm and maintains cap homeostasis of target mRNAs

Article

Author: Mukherjee, Chandrama ; Majumder, Shubhra ; Chakrabarti, Saikat ; Gayen, Anakshi ; Mukherjee, Avik ; Kumar, Krishna

ABSTRACTThe model of RNA stability has undergone a transformative shift with the revelation of a cytoplasmic capping activity that means a subset of transcripts are recapped autonomously of their nuclear counterparts. The present study demonstrates nucleo-cytoplasmic shuttling of the mRNA-capping enzyme (CE, also known as RNA guanylyltransferase and 5′-phosphatase; RNGTT), traditionally acknowledged for its nuclear localization and functions, elucidating its contribution to cytoplasmic capping activities. A unique nuclear export sequence in CE mediates XPO1-dependent nuclear export of CE. Notably, during sodium arsenite-induced oxidative stress, cytoplasmic CE (cCE) congregates within stress granules (SGs). Through an integrated approach involving molecular docking and subsequent co-immunoprecipitation, we identify eIF3b, a constituent of SGs, as an interactive associate of CE, implying that it has a potential role in guiding cCE to SGs. We measured the cap status of specific mRNA transcripts from U2OS cells that were non-stressed, stressed and recovered from stress, which indicated that cCE-target transcripts lost their caps during stress but remarkably regained cap stability during the recovery phase. This comprehensive study thus uncovers a novel facet of cytoplasmic CE, which facilitates cellular recovery from stress by maintaining cap homeostasis of target mRNAs.

01 Jan 2024·European Archives of Oto-Rhino-Laryngology

A novel and independent survival prognostic model for OSCC: the functions and prognostic values of RNA-binding proteins

Article

Author: Yang, Yongtao ; Huang, Chunyu ; Wang, Shanshan ; Li, Limei ; Zhu, Yaomin ; Hu, Xuegang ; Sun, Yingying ; Zhang, Long ; Zhang, Baorong ; Fan, Lina ; Liu, Shuang

BACKGROUNDOral squamous cell carcinoma (OSCC), exhibiting high morbidity and malignancy, is the most common type of oral cancer. The abnormal expression of RNA-binding proteins (RBPs) plays important roles in the occurrence and progression of cancer. The objective of the present study was to establish a prognostic assessment model of RBPs and to evaluate the prognosis of OSCC patients.METHODSGene expression data in The Cancer Genome Atlas (TCGA) were analyzed by univariate Cox regression analysis model that established a novel nine RBPs, which were used to build a prognostic risk model. A multivariate Cox proportional regression model and the survival analysis were used to evaluate the prognostic risk model. Moreover, the receive operator curve (ROC) analysis was tested further the efficiency of prognostic risk model based on data from TCGA database and Gene Expression Omnibus (GEO).RESULTSNine RBPs' signatures (ACO1, G3BP1, NMD3, RNGTT, ZNF385A, SARS, CARS2, YARS and SMAD6) with prognostic value were identified in OSCC patients. Subsequently, the patients were further categorized into high-risk group and low-risk in the overall survival (OS) and disease-free survival (DFS), and external validation dataset. ROC analysis was significant for both the TCGA and GEO. Moreover, GSEA revealed that patients in the high-risk group significantly enriched in many critical pathways correlated with tumorigenesis than the low, including cell cycle, adheres junctions, oocyte meiosis, spliceosome, ERBB signaling pathway and ubiquitin-mediated proteolysis.CONCLUSIONSCollectively, we developed and validated a novel robust nine RBPs for OSCC prognosis prediction. The nine RBPs could serve as an independent and reliable prognostic biomarker and guiding clinical therapy for OSCC patients.

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