更新于：2024-11-01

TUT7 x TUT4

更新于：2024-11-01

基本信息

关联

项与 TUT7 x TUT4 相关的药物

TS-002266

靶点

Bcl-2 x TUT4 x TUT7

作用机制

Bcl-2抑制剂 [+2]

在研机构

Redona Therapeutics, Inc.初创企业

原研机构

Redona Therapeutics, Inc.初创企业

在研适应症

成人急性髓性白血病

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

TUT4/TUT7(Twentyeight-Seven)

靶点

TUT4 x TUT7

作用机制

TUT4 modulators [+1]

在研机构

Redona Therapeutics, Inc.初创企业

原研机构

Redona Therapeutics, Inc.初创企业

在研适应症

肿瘤

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 TUT7 x TUT4 相关的临床结果

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100 项与 TUT7 x TUT4 相关的转化医学

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0 项与 TUT7 x TUT4 相关的专利（医药）

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项与 TUT7 x TUT4 相关的文献（医药）

2024-12-01·International Immunopharmacology

Identification of RNA uridylation subtypes, and the prognostic and therapeutic value of RNA uridylation in systemic lupus erythematosus

Article

作者: Su, Sensen ; Ma, Zhanchuan ; Zhang, Yanli ; Yi, Huanfa ; Wu, Hao

The uridylation of 3'-RNA-a major process in epitranscriptomics- is catalyzed by terminal uridylyl transferases (TUTases), which are involved in multiple diseases and the immune response. Nonetheless, the role of TUTases in systemic lupus erythematosus (SLE) remains unknown. Here we identified increased level of MTPAP and ZCCHC6 and decreased level of PAPD5 and ZCCHC11 in SLE patients from Gene Expression Omnibus (GEO) GSE50772, GSE65391, and GSE121239. The random forest model was applied to screen 4 TUTase candidates (MTPAP, ZCCHC6, PAPD5, and ZCCHC11) to predict the susceptibility of SLE. A nomogram was constructed based on the 4 selected TUTase regulators. Decision curve analysis indicated that patients could benefit from the nomogram. Moreover, based on the 4 differentially expressed genes, individuals with SLE were divided into three patterns (Cluster A-C) using the consensus clustering method. Cluster B was enriched in adaptive immune cells, with the lowest TCE signature expression, manifesting a higher Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) than that in Cluster A and C. whereas, Cluster C was enriched in innate immune cells, with the highest T-cell exhaustion (TCE) signature expression, manifesting lower SLEDAI than that in Cluster B. Clinically, lupus nephritis (LN) patients manifested increased expression of MTPAP and ZCCHC6 and decreased expression of PAPD5 and ZCCHC11 in PBMCs using Quantitative Polymerase Chain Reaction (q-PCR). Immunohistochemistry (IHC) illustrated higher level of ZCCHC6 in the kidneys of LN patients than that in NC. In summary, TUTases could predict the occurrence of SLE and stratify patients based on their immune characteristics, eventually predicting the disease activity and guiding immune therapy.

2024-09-01·Nature Structural & Molecular Biology

Structural basis for activity switching in polymerases determining the fate of let-7 pre-miRNAs

Article

作者: Gilbert, Robert J C ; Zhang, Peijun ; Yi, Gangshun ; Brown, Tom ; Carrique, Loic ; El-Sagheer, Afaf ; Ye, Mingda ; Norbury, Chris J

AbstractTumor-suppressor let-7 pre-microRNAs (miRNAs) are regulated by terminal uridylyltransferases TUT7 and TUT4 that either promote let-7 maturation by adding a single uridine nucleotide to the pre-miRNA 3′ end or mark them for degradation by the addition of multiple uridines. Oligo-uridylation is increased in cells by enhanced TUT7/4 expression and especially by the RNA-binding pluripotency factor LIN28A. Using cryogenic electron microscopy, we captured high-resolution structures of active forms of TUT7 alone, of TUT7 plus pre-miRNA and of both TUT7 and TUT4 bound with pre-miRNA and LIN28A. Our structures reveal that pre-miRNAs engage the enzymes in fundamentally different ways depending on the presence of LIN28A, which clamps them onto the TUTs to enable processive 3′ oligo-uridylation. This study reveals the molecular basis for mono- versus oligo-uridylation by TUT7/4, as determined by the presence of LIN28A, and thus their mechanism of action in the regulation of cell fate and in cancer.

2023-04-21·Communications biology

TUT4/7-mediated uridylation of a coronavirus subgenomic RNAs delays viral replication.

Article

作者: Chen, Shih-Heng ; Martin, Negin P. ; Li, Yin ; Papas, Brian N. ; Morgan, Marcos ; Gupta, Ankit

Coronaviruses are positive-strand RNA viruses with 3' polyadenylated genomes and subgenomic transcripts. The lengths of the viral poly(A) tails change during infection by mechanisms that remain poorly understood. Here, we use a splint-ligation method to measure the poly(A) tail length and poly(A) terminal uridylation and guanylation of the mouse hepatitis virus (MHV) RNAs. Upon infection of 17-CL1 cells with MHV, a member of the Betacoronavirus genus, we observe two populations of terminally uridylated viral transcripts, one with poly(A) tails ~44 nucleotides long and the other with poly(A) tails shorter than ~22 nucleotides. The mammalian terminal uridylyl-transferase 4 (TUT4) and terminal uridylyl-transferase 7 (TUT7), referred to as TUT4/7, add non-templated uracils to the 3'-end of endogenous transcripts with poly(A) tails shorter than ~30 nucleotides to trigger transcript decay. Here we find that depletion of the host TUT4/7 results in an increased replication capacity of the MHV virus. At late stages of infection, the population of uridylated subgenomic RNAs with tails shorter than ~22 nucleotides is reduced in the absence of TUT4/7 while the viral RNA load increases. Our findings indicate that TUT4/7 uridylation marks the MHV subgenomic RNAs for decay and delays viral replication.