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Last update 08 May 2025

PAPD7

Last update 08 May 2025

Basic Info

Synonyms

DNA polymerase sigma, LAK-1, Non-canonical poly(A) RNA polymerase PAPD7

+ [14]

Introduction

Terminal nucleotidyltransferase that catalyzes preferentially the transfer of ATP and GTP on RNA 3' poly(A) tail creating a heterogeneous 3' poly(A) tail leading to mRNAs stabilization by protecting mRNAs from active deadenylation (PubMed:23376078, PubMed:30026317). Also functions as a catalytic subunit of a TRAMP-like complex which has a poly(A) RNA polymerase activity and is involved in a post-transcriptional quality control mechanism. Polyadenylation with short oligo(A) tails is required for the degradative activity of the exosome on several of its nuclear RNA substrates. Has no terminal uridylyltransferase activity, and does not play a role in replication-dependent histone mRNA degradation via uridylation (PubMed:23376078).

Drugs associated with PAPD7

GSK3965193

Target

PAPD5 x PAPD7

Mechanism

PAPD5 inhibitors [+1]

Active Org.

GSK Plc

Originator Org.

GlaxoSmithKline Pharmaceuticals Ltd.

Active Indication

Hepatitis B, Chronic

Inactive Indication-

Drug Highest PhasePhase 1/2

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

AB-161

Target

PAPD5 x PAPD7

Mechanism

PAPD5 inhibitors [+1]

Active Org.

Arbutus Biopharma Corp.

Originator Org.

Arbutus Biopharma Corp.

Active Indication

Hepatitis B

Inactive Indication-

Drug Highest PhasePhase 1

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

US20240376100

Patent Mining

Target

PAPD5 x PAPD7

Mechanism-

Active Org.

Redona Therapeutics, Inc.

Originator Org.

Redona Therapeutics, Inc.

Active Indication

Cardiovascular Diseases [+11]

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with PAPD7

ACTRN12623000074695

/ SuspendedPhase 1

A Double-Blind, Randomized, Placebo-Controlled, Single Dose Study to Investigate the Safety, Tolerability, and Pharmacokinetics of AB-161 Following Oral Administration in Healthy Subjects

Start Date16 Mar 2023

Sponsor / Collaborator

Arbutus Biopharma Corp.

CTR20230241

/ SuspendedPhase 1

一项单中心、双盲、安慰剂对照的首次人体研究，用于评估单次和重复剂量给药 AK0706 片的安全性、耐受性、药代动力学特征及食物影响的 Ia 期临床试验

[Translation] A single-center, double-blind, placebo-controlled, first-in-human study to evaluate the safety, tolerability, pharmacokinetic characteristics and food effects of single and repeated doses of AK0706 tablets in a Phase Ia clinical trial

1、研究 AK0706 片在受试者中的安全性和耐受性，初步评估AK0706 对 QT 间期的影响。 2、评估健康受试者单次口服 AK0706 片和 HBsAg 阳性的 ALT 正常的受试者重复口服 AK0706 的 PK 特征。 3、评估食物对健康受试者口服 AK0706 片的 PK 特征的影响。 4、检测 AK0706 可能的代谢产物类型及主要代谢产物的 PK 特征（如适用）。

[Translation]

1. To study the safety and tolerability of AK0706 tablets in subjects and preliminarily evaluate the effect of AK0706 on the QT interval. 2. To evaluate the PK characteristics of healthy subjects who took AK0706 tablets orally once and subjects who were HBsAg positive and had normal ALT after repeated oral administration of AK0706. 3. To evaluate the effect of food on the PK characteristics of healthy subjects who took AK0706 tablets orally. 4. To detect the possible metabolite types of AK0706 and the PK characteristics of the main metabolites (if applicable).

Start Date16 Feb 2023

Sponsor / Collaborator

Xiamen Amoytop Biotech Co. Ltd.

NCT05330455

/ RecruitingPhase 1/2

Four-part, Randomized, Double-blind (Parts 1, 2A, 3 and 4), Multi-center, Placebo-controlled Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GSK3965193 Monotherapy in Healthy Participants and in Participants Living With Chronic Hepatitis B Infection; and GSK3965193 in Combination With Bepirovirsen in Participants Living With Chronic Hepatitis B Infection

This Phase 1/2a multiple part study is a first time-in-human (FTIH) study designed to evaluate the safety, tolerability, and pharmacokinetics (PK) of single (Part 1) and repeat doses (Part 2) of GSK3965193 in healthy participants. Part 3 will evaluate the ability of GSK3965193 to lower hepatitis B virus surface antigen (HBsAg) in participants living with chronic hepatitis B infection (PLWCHB) and will be given the option to subsequently receive treatment with open label bepirovirsen. Part 4 will evaluate the safety and tolerability of combination therapy with GSK3965193 and bepirovirsen and the potential to effect sustained virologic response in PLWCHB.

Start Date14 Apr 2022

Sponsor / Collaborator

GSK Plc

100 Clinical Results associated with PAPD7

100 Translational Medicine associated with PAPD7

0 Patents (Medical) associated with PAPD7

328

Literatures (Medical) associated with PAPD7

07 Jan 2025·Proceedings of the National Academy of Sciences

TRAMP assembly alters the conformation and RNA binding of Mtr4 and Trf4-Air2

Article

Author: D’Arcy, Sheena ; Zhang, Naifu ; Denson, Joshua M. ; Johnson, Sean J. ; Ball, Darby ; Thompson, Kayla

The TRAMP complex contains two enzymatic activities essential for RNA processing upstream of the nuclear exosome. Within TRAMP, RNA is 3′ polyadenylated by a subcomplex of Trf4/5 and Air1/2 and unwound 3′ to 5′ by Mtr4, a DExH helicase. The molecular mechanisms of TRAMP assembly and RNA shuffling between the two TRAMP catalytic sites are poorly understood. Here, we report solution hydrogen–deuterium exchange data with thermodynamic and functional assays to uncover these mechanisms for yeast TRAMP with Trf4 and Air2 homologs. We show that TRAMP assembly constrains RNA-recognition motifs that are peripheral to catalytic sites. These include the Mtr4 Arch and Air2 zinc knuckles 1, 2, and 3. While the Air2 Arch-interacting motif likely constrains the Mtr4 Arch via transient interactions, these do not fully account for the importance of the Mtr4 Arch in TRAMP assembly. We further show that tRNA binding by single active-site subunits, Mtr4 and Trf4-Air2, differs from the double active-site TRAMP. TRAMP has reduced tRNA binding on the Mtr4 Fist and RecA2 domains, offset by increased tRNA binding on Air2 zinc knuckles 2 and 3. Competition between these RNA-binding sites may drive tRNA transfer between TRAMP subunits. We identify dynamic changes upon TRAMP assembly and RNA-recognition motifs that transfer RNA between TRAMP catalytic sites.

01 Jan 2025·Advanced Science

Unveiling the Mechanism of Deprotonation and Proton Transfer of DNA Polymerase Catalysis via Single‐Molecule Conductance

Article

Author: Zhao, Lihua ; Xu, Yang ; Zhong, Shichao ; Bai, Jingwei ; Guo, Xuefeng ; Liu, Wenzhe ; Yang, Zhiheng

AbstractDNA polymerases (Pols) play important roles in the transmission of genetic information. Although the function and (de)regulation of Pols are linked to many human diseases, the key mechanism of 3′‐OH deprotonation and the PPi formation are not totally clear. In this work, a method is presented to detect the full catalytic cycle of human Pol (hPol β) in graphene‐molecule‐graphene single‐molecule junctions. Real‐time in situ monitoring successfully revealed the spatial and temporal properties of the open and closed conformation states of hPol β, distinguishing the reaction states in the Pols catalytic cycle and unveiling 3′‐OH deprotonation and pyrophosphate (PPi) formation mechanism of hPol β. Proton inventory experiment demonstrated that the rate‐limiting step of PPi formation is deprotonation, which occurs before a reverse conformational change. Additionally, by detecting the acidity (pKa), it is found that MgA‐bound OH− acted as a general base and activated the nucleophile of 3′‐OH, and that acidic residue D190 or D192 coordinated with MgB as a proton donor to PPi. This work provides useful insights into a fundamental chemical reaction that impacts genome synthesis efficiency and Pol fidelity, which the discovery of Pol‐targeting drugs and design of artificial Pols for DNA synthetic applications are expected to accelerated.

31 Dec 2024·RNA Biology

TBP facilitates RNA Polymerase I transcription following mitosis

Article

Author: Teves, Sheila S. ; Kwan, James Z.J. ; Nguyen, Thomas F.

The TATA-box binding protein (TBP) is the sole transcription factor common in the initiation complexes of the three major eukaryotic RNA Polymerases (Pol I, II and III). Although TBP is central to transcription by the three RNA Pols in various species, the emergence of TBP paralogs throughout evolution has expanded the complexity in transcription initiation. Furthermore, recent studies have emerged that questioned the centrality of TBP in mammalian cells, particularly in Pol II transcription, but the role of TBP and its paralogs in Pol I transcription remains to be re-evaluated. In this report, we show that in murine embryonic stem cells TBP localizes onto Pol I promoters, whereas the TBP paralog TRF2 only weakly associates to the Spacer Promoter of rDNA, suggesting that it may not be able to replace TBP for Pol I transcription. Importantly, acute TBP depletion does not fully disrupt Pol I occupancy or activity on ribosomal RNA genes, but TBP binding in mitosis leads to efficient Pol I reactivation following cell division. These findings provide a more nuanced role for TBP in Pol I transcription in murine embryonic stem cells.

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PAPD7

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