摘要:
Riboswitches are structural elements in mRNA that change state when bound by a trigger molecule, and are thus able to regulate gene expression. They can be dissected into two separate domains: one that selectively binds the target (aptamer domain) and another that influences genetic control (expression platform domain). Bacterial glycine riboswitches consist of two tandem aptamer domains which cooperatively bind glycine to regulate the expression of downstream genes. These natural switches are targets for antibiotics and other small molecule therapies. Modified versions of these natural riboswitches can be employed as designer genetic switches that are controlled by specific effector compounds. Disclosed are isolated and recombinant riboswitches, and compositions and methods for selecting and identifying compounds that can activate, inactivate, or block a riboswitch.
摘要:
The preQ1 riboswitch is a target for antibiotics and other small molecule therapies. The preQ1 riboswitch and portions thereof can be used to regulate the expression or function of RNA molecules and other elements and molecules. The preQ1 riboswitch and portions thereof can be used in a variety of other methods to, for example, identify or detect compounds. Compounds can be used to stimulate, active, inhibit and/or inactivate the preQ1 riboswitch. The preQ1 riboswitch and portions thereof, both alone and in combination with other nucleic acids, can be used in a variety of constructs and RNA molecules and can be encoded by nucleic acids.
摘要:
Disclosed is the crystal structure of a GEMM riboswitch from V. cholerae bound to c-di-GMP. The crystal structures show that the RNA binds the ligand within a three helix junction that involves base pairing and extensive base stacking. The symmetric c-di-GMP is recognized asymmetrically with respect to the both the bases and the backbone. Also disclosed are methods of identifying and using compounds and compositions that modulate GEMM riboswitches.
摘要:
The present invention discloses nucleic acid enzymes and deoxyribonucleic acid enzymes capable of cleaving nucleic acid sequences or molecules, particularly RNA, in a site-specific manner, as well as compositions including same. Methods of making and using the disclosed enzymes and compositions are also disclosed.
摘要:
It has been discovered that certain natural mRNAs serve as metabolite-sensitive genetic switches wherein the RNA directly binds a small organic molecule. This binding process changes the conformation of the mRNA, which causes a change in gene expression by a variety of different mechanisms. Modified versions of these natural “riboswitches” (created by using various nucleic acid engineering strategies) can be employed as designer genetic switches that are controlled by specific effector compounds. Such effector compounds that activate a riboswitch are referred to herein as trigger molecules. The natural switches are targets for antibiotics and other small molecule therapies. In addition, the architecture of riboswitches allows actual pieces of the natural switches to be used to construct new non-immunogenic genetic control elements, for example the aptamer (molecular recognition) domain can be swapped with other non-natural aptamers (or otherwise modified) such that the new recognition domain causes genetic modulation with user-defined effector compounds. The changed switches become part of a therapy regimen—turning on, or off, or regulating protein synthesis. Newly constructed genetic regulation networks can be applied in such areas as living biosensors, metabolic engineering of organisms, and in advanced forms of gene therapy treatments.
摘要:
The lysine riboswitch is a target for antibiotics and other small molecule therapies. Compounds can be used to stimulate, active, inhibit and/or inactivate the lysine riboswitch.
摘要:
The present invention discloses deoxyribonucleic acid enzymes—catalytic or enzymatic DNA molecules—capable of cleaving nucleic acid sequences or molecules, particularly RNA, in a site-specific manner, as well as compositions including same. Methods of making and using the disclosed enzymes and compositions are also disclosed.
摘要:
It has been discovered that certain natural mRNAs serve as metabolite-sensitive genetic switches wherein the RNA directly binds a small organic molecule. This binding process changes the conformation of the mRNA, which causes a change in gene expression by a variety of different mechanisms. Modified versions of these natural “riboswitches” (created by using various nucleic acid engineering strategies) can be employed as designer genetic switches that are controlled by specific effector compounds. Such effector compounds that activate a riboswitch are referred to herein as trigger molecules. The natural switches are targets for antibiotics and other small molecule therapies. In addition, the architecture of riboswitches allows actual pieces of the natural switches to be used to construct new non-immunogenic genetic control elements, for example the aptamer (molecular recognition) domain can be swapped with other non-natural aptamers (or otherwise modified) such that the new recognition domain causes genetic modulation with user-defined effector compounds. The changed switches become part of a therapy regimen—turning on, or off, or regulating protein synthesis. Newly constructed genetic regulation networks can be applied in such areas as living biosensors, metabolic engineering of organisms, and in advanced forms of gene therapy treatments.