The SNAPf-tag is a chemical tag that allows rapid and highly specific covalent labeling of proteins even in the full complexity of the cellular environment. The SNAPf-tag has been instrumental to study native RNA-protein complexes at single-molecule resolution in their cellular environment as efficient labeling of the RNAs and proteins of interest is essential for this colocalization single-molecule spectroscopy (CoSMoS) technique. However, removal of excessive benzylguanine dye after the labeling reaction has remained challenging. Here, we describe a strategy to remove excessive benzylguanine dye using SNAPf-tag coated beads as sponges.
Keywords: CoSMoS; Colocalization single-molecule spectroscopy; Protein labeling; RNA spectroscopy; RNA-protein complex; RNP; Single-molecule fluorescence microscopy; Single-molecule spectroscopy; TIRF microscopy.