Abstract: Provided herein are compositions and methods for regulating protein translation. The compositions include a cap-conjugated oligonucleotide comprising an m7G cap or a variant or analog thereof conjugated to an oligonucleotide, wherein the oligonucleotide is capable of specifically hybridizing with a target sequence in an RNA molecule. The disclosure further provides methods of regulating translation of an mRNA in a cell, the method comprising contacting the cell with a cap-conjugated oligonucleotide comprising an m7G cap or a variant or analog thereof conjugated to an oligonucleotide, wherein the oligonucleotide comprises a sequence capable of specifically hybridizing with a target sequence in an RNA molecule.

Abstract: Provided are RNA recognition complexes that include an RNA-targeting agent; and a coronavirus-derived protein. In some embodiments, the RNA recognition complex further includes a linker. In some embodiments, the RNA-targeting agent includes CRISPR/Cas9 components (e.g., a Cas9 protein, a Cas 13b protein, or a Cas 13d protein). Also provided herein are methods of upregulating gene expression of a target RNA that include delivering a RNA recognition complex into a cell, wherein the RNA recognition complex comprises a RNA-targeting agent, and a coronavirus-derived protein, and wherein the RNA recognition complex binds to the target RNA and upregulates gene expression of the target RNA in the cell.

Abstract: Provided are methods of inhibiting activity of a RNA binding protein in a cell that include (a) generating a RNA binding N protein (RBP) binding agent comprising an RNA molecule comprising a binding site for the RNA binding protein; and (b) delivering the RBP binding agent into the cell, wherein the RBP binding agent binds to the RNA binding protein, thereby inhibiting the activity of the RNA binding protein in the cell.

Abstract: Provided herein are compositions and methods for regulating protein translation. The compositions include a Cas polypeptide and a capped-sgRNA that includes (i) an m7G cap or an analog thereof; (ii) a spacer capable of specifically hybridizing with a target sequence in an RNA molecule; and (iii) a direct repeat capable of binding to the Cas polypeptide. The disclosure further provides methods of regulating translation of an mRNA in a cell, the method comprising contacting the cell with a nucleic acid comprising (a) a sequence encoding a Cas polypeptide; and (b) a sequence encoding a capped-sgRNA comprising (i) an m7G cap or analog thereof; (ii) a spacer capable of specifically hybridizing with a target sequence in an RNA molecule; and (iii) a direct repeat capable of binding to the Cas polypeptide.

Abstract: Provided herein ar compositions and methods for regulating protein translation. The compositions include a cap-conjugated oligonucleotide comprising an m7G cap or a variant or analog thereof conjugated to an oligonucleotide, wherein the oligonucleotide is capable of specifically hybridizing with a target sequence in an RNA molecule. The disclosure further provides methods of regulating translation of an mRNA in a cell, the method comprising contacting the cell with a cap-conjugated oligonucleotide comprising an m7G cap or a variant or analog thereof conjugated to an oligonucleotide, wherein the oligonucleotide comprises a sequence capable of specifically hybridizing with a target sequence in an RNA molecule.

Abstract: Described herein are compositions, systems, methods, and kits utilizing RNA binding protein fusions, such as CRISPR-Cas protein fusions comprising a guide nucleotide sequence-programmable RNA binding protein, and a translation modifier protein. Also, described herein are compositions, systems, methods, and kits utilizing CRISPR-Cas associated RNA fusions comprising a guide nucleotide sequence-programmable RNA and an internal ribosome entry site (IRES). The compositions, systems, methods, and kits described herein are useful to upregulate or downregulate mRNA translation.