Acc. Chem. Res. XXXX, XXX, XXX−XXX "minimalist tag" containing a series of bio-orthogonal tags. A set of aff inity-based probes for BRD4 inhibitors was created and investigated for interactome studies, resulting in novel off-target discovery.

Proximity labeling techniques are emerging highthroughput methods for studying protein-protein, protein-RNA, and protein-DNA interactions with temporal and spatial precision. Proximity labeling methods take advantage of enzymes that can covalently label biomolecules with reactive substrates. These labeled biomolecules can be identified using mass spectrometry or next-generation sequencing. The main advantage of these methods is their ability to capture weak or transient interactions between biomolecules. Prox-imity labeling is indispensable for studying organelle interactomes. Additionally, it can be used to resolve spatial composition of macromolecular complexes. Many of these methods have only recently been introduced; nonetheless, they have already provided new and deep insights into the biological processes at the cellular, organ, and organism levels. In this paper, we review a broad range of proximity labeling techniques, their development, drawbacks and advantages, and implementations in recent studies.

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RNA is an intermediate player between DNA transcription and protein translation. RNAs also interact with other macromolecules, metabolites and regulate their fate. The emerging number of RNA identification expanded new...