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更新于：2025-01-23

核糖核酸酶

更新于：2025-01-23

基本信息

别名-

简介-

关联

项与核糖核酸酶相关的药物

OKG-0303

靶点

核糖核酸酶

作用机制

核糖核酸酶调节剂

在研机构

Okogen, Inc.初创企业

原研机构

Okogen, Inc.初创企业

在研适应症

急性结膜炎

非在研适应症-

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

Tirandamycin

靶点

核糖核酸酶

作用机制

Ribonuclease inhibitors

在研机构

The Upjohn Co.

原研机构

The Upjohn Co.

在研适应症

细菌感染

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

Theranase

靶点

核糖核酸酶

作用机制

核糖核酸酶调节剂

在研机构-

原研机构

Sarossa Capital Ltd.

在研适应症-

非在研适应症

淋巴瘤

最高研发阶段终止

首次获批国家/地区-

首次获批日期1800-01-20

100 项与核糖核酸酶相关的临床结果

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100 项与核糖核酸酶相关的转化医学

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0 项与核糖核酸酶相关的专利（医药）

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1,606

项与核糖核酸酶相关的文献（医药）

2024-11-29·Reproduction

Seminal proteoforms from bulls with contrasting semen freezability: a story deciphered by top-down mass spectrometry

Article

作者: Memili, Erdogan ; Guedes de Azevedo Viana, Arabela ; Di Silvestre, Dario ; Machado-Neves, Mariana ; Gomes, Fabio Pereira ; Topper, Einko ; Diedrich, Jolene ; Moura, Arlindo Alencar ; Yates, John R ; Kaya, Abdullah

In briefBovine sperm and seminal plasma (SP) proteoform atlas was characterized using top-down proteomics. Specific post-translational modifications and protein truncations correlated with semen freezability, with potential links to sperm functional processes.AbstractTop-down proteomics was employed to construct a proteoform atlas of sperm and SP from bulls with low semen freezability (LF) and high semen freezability (HF). Sperm and seminal proteins were fractionated by tandem size exclusion chromatography (<30 kDa) and analyzed by reversed-phase liquid chromatography-tandem mass spectrometry. This approach enabled identification of 299 SP (from 46 families) and 267 sperm proteoforms (from 139 families). Seventy proteoforms belonging to beta-defensin 10, c-type natriuretic peptide (NPPC), caltrin, seminal ribonuclease, osteopontin and binder of sperm protein (BSP) 3 families were unique to HF bulls’ SP. LF seminal proteins had 77 unique proteoforms, including caltrin, NPPC, osteopontin, BSP3, serpin family A member 5 and β-NGF families. Proteoform families of SP in HF and LF bulls were related to Ca2+ uptake, capacitation, acrosome reaction, sperm protection, fertilization and proteolytic processes. Thirty-three proteoforms of NPPC, caltrin and cylicin-2 families were upregulated in HF sperm. Twenty-two proteoforms of caltrin, cylicin-2, adenosine triphosphate (ATP) synthases and malate dehydrogenase families were among those upregulated in LF sperm. Truncated and acetylated histone H2A and non-truncated and acetylated c-Myc-binding protein were prevalent in LF sperm. Cylicin-2 proteoforms were observed in HF and LF sperm, and truncated glyceraldehyde-3-phosphate dehydrogenases were observed only in HF sperm. In silico analyses indicated the enrichment of mitochondrial metabolic pathways in HF sperm, including fatty acid metabolism and TCA cycle. Our study provides an unprecedented description of the bovine SP and sperm proteoforms. Post-translational processing appears to define the bioproperties of semen proteins and their associations with sperm cryoresistance.

2024-11-07·Nature

Structural basis of archaeal FttA-dependent transcription termination

Article

作者: Kaelber, Jason T. ; Ebright, Richard H. ; Sanders, Travis J ; Wang, Chengyuan ; Ulisse, Paul ; Santangelo, Thomas J ; Molodtsov, Vadim ; Santangelo, Thomas J. ; Kuznedelov, Konstantin ; Kaelber, Jason T ; Ebright, Richard H ; Marshall, Craig J ; Wenck, Breanna R. ; Firlar, Emre ; Sanders, Travis J. ; Marshall, Craig J. ; Miao, Xinyi ; You, Linlin ; Wenck, Breanna R

The ribonuclease FttA (also known as aCPSF and aCPSF1) mediates factor-dependent transcription termination in archaea^1-3. Here we report the structure of a Thermococcus kodakarensis transcription pre-termination complex comprising FttA, Spt4, Spt5 and a transcription elongation complex (TEC). The structure shows that FttA interacts with the TEC in a manner that enables RNA to proceed directly from the TEC RNA-exit channel to the FttA catalytic centre and that enables endonucleolytic cleavage of RNA by FttA, followed by 5'→3' exonucleolytic cleavage of RNA by FttA and concomitant 5'→3' translocation of FttA on RNA, to apply mechanical force to the TEC and trigger termination. The structure further reveals that Spt5 bridges FttA and the TEC, explaining how Spt5 stimulates FttA-dependent termination. The results reveal functional analogy between bacterial and archaeal factor-dependent termination, functional homology between archaeal and eukaryotic factor-dependent termination, and fundamental mechanistic similarities in factor-dependent termination in bacteria, archaea, and eukaryotes.

2024-10-01·Biochimica et Biophysica Acta (BBA) - General Subjects

Keratinocyte and myeloid MCPIP1 have distinct roles in maintaining skin homeostasis

Article

作者: Rumienczyk, Izabela ; Mikula, Michal ; Szukala, Weronika ; Zawada, Roza ; Goryca, Krzysztof ; Lichawska-Cieslar, Agata ; Jura, Jolanta

The skin is a complex organ, and the intricate network between keratinocytes and immune cells is critical for ensuring skin function. Monocyte chemotactic protein-1-induced protein 1 (MCPIP1) is a ribonuclease that functions as a key negative modulator of inflammation. We previously reported that conditional deletion of MCPIP1 in keratinocytes (Mcpip1^EKO) impairs skin integrity in adult mice. A similar phenotype was observed following the depletion of MCPIP1 in the myeloid compartment (Mcpip1^MKO). The aim of this study was to develop a keratinocyte and myeloid double-MCPIP1 knockout mouse model to clarify the specific roles of myeloid and epidermal MCPIP1 in skin biology. Histological analyses indicated that the skin morphology changed after depletion of MCPIP1 in cells of myeloid origin as well as in keratinocytes. The thicknesses of the epidermal and subcutaneous fat layers increased in the mice with a loss of epidermal MCPIP1, whereas the loss of myeloid MCPIP1 had the opposite effect. In addition, both types of mice showed opposite responses to stimulation with 12-O-tetradecanoylphorbol-13-acetate. Transcriptomic profiling of whole-skin lysates revealed some common target transcripts in all the knockout mice. Further analyses revealed that distinct pathways are modulated following the loss of epidermal or myeloid MCPIP1. The skin morphology and inflammatory phenotype of keratinocyte and myeloid double-MCPIP1 knockout mice resembled those of mice with only keratinocyte-specific knockout of MCPIP1. Overall, myeloid and epidermal MCPIP1 play important but distinct roles in the modulation of skin-related processes.

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