Nascent chain libraries probing PF-06446846-dependent stalling

This study performed ribosome display of a nascent chain library to determine sequence determinants of PF-06446846 (PF846) dependent ribosome stalling. Several four-codon stretches of a previously-identified stalling sequence on the CDH1 mRNA were subjected to saturation mutagenesis and successful stalling members were isolated by an affinity tag on the nascent chain. This study aims to uncover determinants of the unusual sequence specificity displayed by PF846. A detailed understanding of the PF846 stalling mechanism lays the foundation for targeted protein knockdown by sequence-specific small molecule ribosome stalling.