Pumilio Domain-based Modular Protein Architecture for RNA Binding

摘要

A programmable modular protein architecture for RNA binding comprises a set of modules, derived from RNA-binding protein Pumilio, that can be concatenated into chains of varying composition and length. When bound into a chain, each module has a preferred affinity for a specific RNA base. The chains can bind arbitrary RNA sequences with high specificity and fidelity by varying the sequence of modules within the chains. Each module contains at least 6 amino acids, with the amino acids in positions 1 and 5 providing the preferred affinity for the specific base, and the amino acid at position 2 serving as a stacking unit between concatenated modules. The modules may have four canonic forms, each having a preferred affinity for a different base and characterized by the base with which it has affinity, the two amino acids that provide the affinity, and the amino acid that serves as a stacking unit.

主权项

1. A modular protein architecture for RNA binding, comprising a set of protein modules derived from the RNA-binding protein Pumilio, wherein the protein modules can be concatenated into chains of varying composition and length, wherein each protein module, when bound into a chain, has a preferred affinity for a specific target RNA base, wherein the concatenated chains of protein modules provide the ability to bind arbitrary RNA sequences, with high specificity and fidelity, by varying the sequence of the protein modules within the chains, and wherein each protein module contains at least 6 amino acids selected such that the amino acids in positions 1 and 5 provide the preferred affinity of the protein module for the specific RNA base and the amino acid at position 2 serves as a stacking unit between concatenated modules.