113 results about "RNA-Binding Motif" patented technology

The invention provides a DNA binding protein and RNA binding protein classification method based on ESM-2 and a dual-path neural network, and particularly relates to a staged classification method combining the ESM-2 and the dual-path neural network, which is called DRBP-EDP. In the first stage training, the protein sequence is classified as a nucleic acid binding protein or a non-nucleic acid binding protein; further classifying the nucleic acid binding protein as a DNA binding protein or an RNA binding protein in the second stage of training; meanwhile, a fine data set construction method is further constructed, so that a high-quality protein classification data set is created, through the method, the DRBP-EDP model obtains good performance, the classification accuracy of the nucleic acid binding protein and the non-nucleic acid binding protein in the first stage is 90.03%, and the classification accuracy of the non-nucleic acid binding protein in the second stage is 90.03%. In the second stage, the classification accuracy of the DNA binding protein and the RNA binding protein is 89.56%, a new insight and a new method are provided for protein classification, an innovative tool is provided for research on protein functions, and therefore a new opportunity is provided for development of life science.

The present disclosure provides compositions and methods for the targeted modification of RNA molecules by RNA prime editing. The compositions and methods may be conducted invitro or in vivo within cells (e.g., human cells) for the therapeutic correction of disease-causing mutations and / or installation of motifs or mutations in RNA molecules of interest as a tool for scientific research. The disclosure provides compositions and methods for conducting RNA prime editing of a target RNA molecule (e.g., an RNA transcript) that enables the incorporation of one or more nucleotide changes and / or targeted mutagenesis of a target RNA molecule. The nucleotide change can include a single-nucleotide change, an insertion of one or more nucleotides, or a deletion of one or more nucleotides. More in particular, the disclosure provides a variety of configurations of the RNA prime editors each comprising a nucleic acid programmable RNA binding proteins (napRNAbp), such as Cas13, and an RNA-dependent RNA polymerase (RDRP), which are provided as fusion proteins or which can be separately provided in trans. The RNA prime editors are guided to a target RNA site by a guide RNA, which can be a rpegRNA that includes a template region for the synthesis of an RNA sequence to be installed on the RNA molecule attached to an available 3′ terminus. In others embodiments, the RNA template can be provided in trans.

The present disclosure provides compositions and methods for the targeted modification of RNA molecules by RNA prime editing. The compositions and methods may be conducted invitro or in vivo within cells (e.g., human cells) for the therapeutic correction of disease-causing mutations and / or installation of motifs or mutations in RNA molecules of interest as a tool for scientific research. The disclosure provides compositions and methods for conducting RNA prime editing of a target RNA molecule (e.g., an RNA transcript) that enables the incorporation of one or more nucleotide changes and / or targeted mutagenesis of a target RNA molecule. The nucleotide change can include a single-nucleotide change, an insertion of one or more nucleotides, or a deletion of one or more nucleotides. More in particular, the disclosure provides a variety of configurations of the RNA prime editors each comprising a nucleic acid programmable RNA binding proteins (napRNAbp), such as Cas13, and an RNA-dependent RNA polymerase (RDRP), which are provided as fusion proteins or which can be separately provided in trans. The RNA prime editors are guided to a target RNA site by a guide RNA, which can be a rpegRNA that includes a template region for the synthesis of an RNA sequence to be installed on the RNA molecule attached to an available 3′ terminus. In others embodiments, the RNA template can be provided in trans.

The present invention relates to antisense oligonucleotides which are complementary to conserved TDP-43 binding sites on pre-mRNA transcripts, which are capable of restoring RNA binding protein function in the processing of multiple independent mRNAs in TDP-43 depleted cells. The contiguous nucleotide sequence of the antisense oligonucleotides comprise 2′-O-methoxyethyl-RNA (2′-MOE) nucleosides and the antisense oligonucleotides are attached to cholesterol moieties.

The invention discloses construction and application of a targeted exosome chimeric antigen receptor molecule for treating HIV (human immunodeficiency virus) infection, and belongs to the technical field of biological medicines. According to the invention, the mRNA for coding the anti-HIV CAR is directionally packaged into the targeting exosome. Nanometer antibody sequences of CD3, CD4 and CD8 < + > T receptors on targeted T cells are fused to the N terminal of LAMP-2B to construct a specific targeting plasmid, so that targeting peptides are expressed on the surface of an exosome membrane, expression plasmids containing RNA binding protein L7A and exosome tag protein CD63 are constructed, and HEK293F cells are co-transfected by the expression plasmids and CAR plasmids containing C / D box to obtain the exosome loaded with CAR mRNA and targeted to the T cells. When the exosome is incubated with PBMC (peripheral blood mononuclear cells) in vitro or is transfused back into a humanized mouse body, human CAR-T cells can be constructed, and the exosome has remarkable activity of killing virus infected cells.

The present disclosure relates to methods of identifying RNA targets of RNA binding proteins. In aspects, the disclosure relates to a method of identifying RNA molecules bound by RNA binding proteins. Some embodiments of the present disclosure relate to a method that can definitively identify direct RNA-target interactions with targeted proteins without the requirement for immunoprecipitation or gel extraction. In some embodiments, the method may include combining multiple antibodies in the same sample.

The invention discloses an RNA (Ribonucleic Acid) binding protein enrichment analysis method based on single cell expression profile data, which comprises the following steps of: writing an interactive online Web application program by using Shiny, carrying a data visualization tool, and using an RBP (Reactive Binding Protein)-gene database as a database; the method is specially designed for single cell data, different single cell data can be integrated for enrichment analysis, and expression profiles and RBP dynamic changes in single cells can be effectively captured and analyzed; rBP enrichment analysis is customized for single cell data, a single group and multiple groups of single cell expression data are preprocessed, including normalization processing, and a statistical model is used to evaluate enrichment significance at each time point, so that the analysis accuracy and biological correlation are improved; a dynamic visualization tool is provided, the dynamic visualization tool comprises a customizable network diagram, an interactive bar diagram and detailed table display, and a user can adjust a plurality of parameters of a view according to needs and directly download images and data from an interface.

Provided are methods of modulating gene expression of a target RNA in a cell comprising (a) recruiting a modulation unit, wherein the modulation unit comprises an RNA binding protein (RBP), an exogenous RNA binding moiety, and a gene-editing agent; (b) delivering the modulation unit into the cell; and (c) detecting change in the target RNA translation, wherein the modulation unit modulates gene expression of the target RNA in the cell.

The invention discloses an effect and application of RNA (Ribonucleic Acid) binding protein in skeletal muscle injury repair, and relates to the technical field of new application of medicines. A large number of experiments show that the RNA binding protein ARPP21 is up-regulated in the repair process after skeletal muscle injury. After the ARPP21 is knocked out, the repair capability of the mouse after skeletal muscle injury is weakened, and myoblast differentiation is inhibited. And when the ARPP21 is over-expressed, early migration of mouse myoblast differentiation can be promoted. Therefore, the ARPP21 plays an important regulating role in regeneration and repair after the skeletal muscle injury, can be used for preparing a medicine for regeneration and repair after the skeletal muscle injury, and provides a new clue and strategy for rehabilitation treatment after the skeletal muscle injury.

The invention discloses application of RNA (Ribonucleic Acid) binding protein CsdA in regulation and control of secondary metabolites of fungi. The invention provides application of RNA (Ribonucleic Acid) binding protein CsdA or related biological materials thereof in regulation and control of fungus secondary metabolites. The RNA binding protein CsdA is a protein of which the amino acid sequence is as shown in SEQ ID No. 3 or SEQ ID No. 2 or a homologous protein of the protein of which the amino acid sequence is as shown in SEQ ID No. 3 or SEQ ID No. 2. The invention is helpful for excavating natural products with medicinal activity in fungi, is helpful for developing new anti-fungal infection drug targets, and reduces the probability of fungal infection.

The present invention provides novel RNA base editing compositions, systems, methods and uses. Guide RNAs for site-specific RNA editing of RNA encoding transcriptional coactivators YAP1 or TAZ are provided, and compositions and systems comprising the same with a programmable RNA binding protein (e.g. a Cas protein) and / or a base editor. Methods for RNA editing of YAP1 or TAZ are also provided. RNA editing of YAP1 or TAZ is used for targeting phosphorylation sites, and activating transcription of proteins in regenerative therapy for treating cardiac disease.

The invention provides a method for crosslinking and marking biomolecules in living animals based on photocatalysis. According to the method, the hydrophilic up-conversion nano composite material and the photosensitizer are in contact with the biological sample to be detected, and the target position of the biological sample to be detected is subjected to near-infrared light irradiation, so that the RNA-RNA binding protein compound is formed in situ at the target position of the biological sample to be detected, and the biological sample is obtained. Especially in situ crosslinking of RNA and RNA binding proteins in an organism. On the basis of the cross-linking method, marking, enrichment and analysis of all kinds of RNA-RNA binding protein compounds and RNA binding proteins can be realized by further matching with a compound as shown in a formula 1, and the method has broad spectrum; meanwhile, pollution caused by cross-linking of protein and protein and cross-linking of DNA and protein is effectively avoided, and high specificity is achieved.

This invention discloses a method and system for predicting RNA binding protein binding sites on RNA without targeting, relating to the field of bioinformatics. The method includes the following steps: acquiring raw RNA structure data; expanding and filtering the preprocessed data; training an RNA analysis model using the filtered data; processing the RNA to be analyzed using the trained RNA analysis model, calculating the probability that each nucleotide is single-stranded, and obtaining a structure score; identifying low-accessibility regions based on the difference between the structure score output by the RNA analysis model and the structure score calculated by the original method; and identifying potential RNA binding protein binding sites by comparing the signal difference with that of the original method in a single RNA structure detection experiment. This invention utilizes the STONE method to improve the accuracy of RNA structure analysis in low-accessibility regions, and uses the improved difference to infer RBP binding sites, thereby improving the accuracy of RBP binding site identification.

According to the RNA binding protein HuR inhibitor and the anti-fibrosis application thereof, the compound provided by the invention has obvious inhibitory activity on HuR protein, has a good anti-renal fibrosis effect, can obviously reduce protein and mRNA expression levels of fibronectin (FN1) and alpha-smooth muscle actin (alpha-SMA), can improve renal function impairment, and can be used for preparing the anti-fibrosis medicine for treating renal fibrosis. The levels of blood urea nitrogen (BUN) and creatinine (Cr) which are commonly used for evaluating the renal function are reduced, and the compound can be used for preparing the medicine for treating the chronic kidney disease.

The invention provides an application of DCTPP1 in detection of an auditing abortion kit, relates to the technical field of target spot diagnosis, and particularly provides an application of DCTPP1 as a target spot in preparation of an auditing abortion detection product, and an experimental result shows that DCTPP1 is one of key genes for auditing abortion. Specifically, after the DCTPP1 is knocked down from a human embryo trophoblast cell line HTR8 / SVneo, compared with a control group, the reduction of the DCTPP1 can cause more cell oxidation stress increase, and cell viability is reduced 24 hours later, and finally cell apoptosis occurs; in the mechanism, the DCTPP1 interacts with the RNA binding protein AUF1, and the reduction of the DCTPP1 causes the increase of oxidative stress of human embryo trophoblastic cells through the AUF1, so that apoptosis is caused. Experimental results in the application show that DCTPP1 is one of key genes for auditing abortion, and cell apoptosis can be finally caused by destroying the function of DCTPP1 in embryonic trophoblast cells through technologies such as transfection of specific siRNA and the like. In addition, the DCTPP1 knocked-down embryo trophoblast cells can be subjected to apoptosis, and the DCTPP1 knocked-down embryo trophoblast cells are one of useful genes for detecting and auditing abortion.

The present application provides a kind of brown planthopper RNA binding protein NlRBP gene inhibitor and application, the NlRBP gene inhibitor is the dsRNA capable of inhibiting brown planthopper NlRBP gene expression, the nucleotide sequence of the dsRNA is as shown in SEQ ID NO.3.The present application also provides the application of the above-mentioned brown planthopper RNA binding protein NlRBP gene inhibitor in the prevention and treatment of brown planthopper.The prevention and treatment of brown planthopper is to inhibit the survival rate of brown planthopper.The survival rate of brown planthopper is realized by inhibiting the expression of brown planthopper RNA binding protein NlRBP gene.The present application also provides the application of the above-mentioned dsRNA in preparation product.The present application provides a new prevention and treatment strategy and target for brown planthopper prevention and treatment, establishes the technology based on RNAi green control brown planthopper, provides foundation and reference for the precision, sustained pest control of brown planthopper, and has good application prospect.

Disclosed are methods, systems, and computer readable media for predicting interactions for RNA sequences, including long noncoding RNA (IncRNA), which can be used, for example, as biomarkers. In an example method of predicting one or more binding sites between a ribonucleotide (RNA) sequence and a RNA binding protein, the method includes at a computing platform including at least one processor and memory: preparing sequence data for a plurality of overlapping RNA segments derived from a target sequence; inputting the sequence data for the plurality of overlapping RNA segments into a machine learning model trained to predict a probability of an interaction between a RNA sequence and a RNA binding protein occurring in a RNA sequence; outputting from the machine learning model one or more segments in the sequence data for the plurality of overlapping RNA segments falling above a probability threshold indicative of a region of interaction between a RNA sequence and a RNA binding protein; and predicting one or more binding sites between a RNA sequence and a RNA binding protein in the sequence data for the plurality of overlapping RNA segments derived from the target sequence based on the output from the model.

The present invention includes compounds and compositions, and methods of use thereof for modulating an RNA transcript, or a precursor, isoform, fragment, or mutant thereof by degradation of the RNA transcript via recruitment or binding of one or more decay factors (e.g., an RNA binding protein).

The present application provides a fusion protein comprising an anti-CD3 single-domain antibody, an exosome protein CD63 and an RNA binding protein, and uses thereof. The fusion protein of the present application achieves the effects of treating cancer, immune regulation and activating immune cells through various efficacy experiments.

The invention discloses a targeted enrichment method for proteome. According to the cell nucleus targeted RNA binding protein enrichment reagent, one end is provided with a furocoumarin group, the other end is provided with a cell nucleus targeted group, and the other end is provided with biotin; the enrichment or identification of the RNA binding protein in the cell nucleus can be carried out. The method for enriching the nucleus-targeted RNPs by adopting the nucleus-targeted RNA binding protein enrichment reagent comprises the following steps: firstly, adding the nucleus-targeted RNA binding protein enrichment reagent into cells for co-incubation, then, irradiating a cell incubation system by adopting ultraviolet light with the wavelength of 254nm, and then, irradiating the cell incubation system by adopting ultraviolet light with the wavelength of 365nm, then carrying out cracking to obtain a cracking solution; incubating the lysis solution and streptavidin magnetic beads, and finally collecting the magnetic beads enriched with the cell nucleus RNPs, so that the cell nucleus targeted RNPs are enriched. According to the method, the cell nucleus positioning of the reagent can be efficiently realized, the RBPs enrichment selectivity and the negative electrode efficiency are improved, and the varieties of RNPs obtained through enrichment are more comprehensive.

This invention discloses a novel application of the RNA-binding protein HNRNPA1 in regulating copper death in synovial fibroblasts of rheumatoid arthritis (RA-FLS). Overexpression of HNRNPA1 recognizes and binds to the m6A modification site of SLC3A2 mRNA, enhancing its transcript stability, restoring the expression of SLC3A2 and copper death-related proteins, reducing MDA levels, increasing copper ion concentration and the activity of antioxidant enzymes SOD and POD, thereby repairing mitochondrial ultrastructural damage, inhibiting abnormal cell proliferation, and inducing apoptosis. Reversal experiments confirmed that knocking down SLC3A2 reverses the above effects, indicating that SLC3A2 is a core downstream target of HNRNPA1-mediated copper death. This invention reveals for the first time the decisive role of the HNRNPA1-SLC3A2-copper death axis in the pathological phenotype of RA-FLS, providing a new target for molecular intervention in rheumatoid arthritis.

The present invention includes compounds and compositions, and methods of use thereof for modulating an RNA transcript, or a precursor, isoform, fragment, or mutant thereof by degradation of the RNA transcript via recruitment or binding of one or more decay factors (e.g., an RNA binding protein).

The present invention includes compounds and compositions, and methods of use thereof for modulating an RNA transcript, or a precursor, isoform, fragment, or mutant thereof by degradation of the RNA transcript via recruitment or binding of one or more decay factors (e.g., an RNA binding protein).

The present disclosure provides methods for simultaneously identifying dynamic and disease- relevant RNA binding protein (RBP)-RNA interaction (PRI) sites throughout the transcriptome at single-nucleotide resolution. The methods disclosed herein recapitulate the PRI profiles obtained with several different conventional PRI methods with several orders of magnitude improvement in efficiency in a single assay and allow identification of the specific RBP bound at the PRI.

The invention belongs to the technical field of biological genes, and discloses a method for identifying RNA interaction protein based on a Turbo ID technology and an MCP / MS2 system, the method can be used for identifying protein interacting with RNA in vitro or in vivo, and the method specifically comprises the following steps: firstly, respectively constructing RNA expression vectors inserted with MS2 tags, then constructing fusion protein vectors expressing MCP-Turbo ID, and finally constructing fusion protein vectors for expressing MCP-Turbo ID; the method comprises the following steps of: inserting RNA (Ribonucleic Acid) into an MS2 tag, transgenosis into a plant receptor by utilizing an agrobacterium tumefaciens mediated genetic transformation method to obtain a transgenic plant material expressing MCP-Turbo ID, combining the RNA inserted with the MS2 tag with the MCP-Turbo ID in vivo / in vitro by utilizing a hybridization or in-vitro incubation method, further enabling the Turbo ID to be adjacent to the RNA, biotinylating the RNA binding protein, and obtaining a transgenic plant material expressing the MCP-Turbo ID. And then enriching biotinylated protein by adopting streptavidin magnetic beads, and identifying and analyzing through Western Blot and mass spectrometry. The method not only solves the problem that the interaction protein of specific RNA in a living cell environment cannot be effectively identified in the prior art, but also can capture a transient or low-affinity RNA-protein interaction relationship.

Provided herein are nuclear expressed antisense RNAs for interfering with a target repetitive RNA, the nuclear expressed antisense RNA comprising: (a) an oligonucleotide encoding an RNA-targeting guide comprising a sequence complementary to the target repetitive RNA; and (b) an oligonucleotide encoding a RNA binding protein (RBP) / ribonucleoprotein (RNP)-recruiting motif.

The application discloses a peanut protein content related molecular marker and related application. The molecular marker is located at 95485614bp-95490150bp of peanut chromosome 1, is an RNA binding protein KH domain-containing protein gene, and a SNP site (T / A) is detected at 95487145bp, namely, the gene is on the complementary strand, the position (CDS sequence 1229th base) on the gene sequence is A in the low-protein peanut group and T in the high-protein peanut group, and a mutation from lysine to isoleucine (protein 410th amino acid) is caused. The application provides a new marker for peanut high-protein resource molecular marker assisted selection for the first time, and has very important significance for high-protein peanut resource screening and high-protein peanut new variety breeding.

The invention features compositions and methods useful for targeting and activating translation, for example, non-canonical translation, in cancer cells.

The application discloses a kind of targeted exosome chimeric antigen receptor molecules for treating HIV infection and its application, belong to the field of biological medicine technology.The application is packaged into targeted exosome by coding anti-HIV CAR mRNA directionally.The nano antibody sequence of targeted CD3, CD4, CD8+T receptor on T cell is fused to the N-terminal of LAMP-2B to construct specific targeting plasmid, so that the targeted peptide is expressed on the surface of exosome membrane, the expression plasmid containing RNA binding protein L7A and exosome tag protein CD63 is constructed, and the exosome loaded with CAR mRNA and targeted to T cell is obtained by three-plasmid co-transfection of HEK293F cells containing C / D box CAR plasmid.The exosome can construct human CAR-T cell when incubated with PBMC in vitro or back into humanized mouse in vivo, and has significant killing virus infected cell activity.

The invention belongs to the field of biological medicine, and particularly discloses a pharmaceutical application of an AR agonist based on bioinformatics targeted screening in sepsis sarcopenia, and the core is that the AR agonist Ostarine is adopted to specifically activate muscle AR and improve SIS through subcutaneous injection administration in the acute stage (within 5 days) of sepsis. The mechanism comprises the following steps: (1) recovering skeletal muscle protein synthesis (up-regulating p-AKT / p-mTOR) and decomposing metabolic balance (down-regulating Atrogin-1 / MuRF1); (2) promoting the expression of a polyamine biosynthetic gene (AMD / ODC1 / SMOX); and (3) adjusting the ratio of fast and slow muscle fibers (promoting MyoD and inhibiting MHC I and TnI-flow). Experiments show that Ostarine (5mg / kg) can significantly improve the survival rate, muscle weight and grip strength of sepsis mice within 5 days and reverse amyotrophy. In addition, the invention provides an SIS drug screening method based on the RNA binding protein Hnrnpa1 (regulating AR pre-mRNA). The method is easy and convenient to operate and high in targeting performance, and a new strategy is provided for treatment of sepsis sarcopenia.