Gene

Protein–protein interaction

Context (archaeology)

Biology

XIST

Cas9

X chromosome

Long non-coding RNA

CRISPR

RNA-binding protein

Computational biology

MALAT1

Paleontology

Genetics

X-inactivation

Guide RNA

Nature Methods

We have developed CRISPR-assisted RNA–protein interaction detection method (CARPID), which leverages CRISPR–CasRx-based RNA targeting and proximity labeling to identify binding proteins of specific long non-coding RNAs (lncRNAs) in the native cellular context. We applied CARPID to the nuclear lncRNA XIST, and it captured a list of known interacting proteins and multiple previously uncharacterized binding proteins. We generalized CARPID to explore binders of the lncRNAs DANCR and MALAT1, revealing the method’s wide applicability in identifying RNA-binding proteins. CARPID uses CRISPR technology to navigate biotin ligase to specific lncRNAs, which allows proximal labeling and thus the querying of RNA–protein interactions in living cells.

CRISPR-assisted detection of RNA–protein interactions in living cells