Datasets

Title	Selective stalling of human translation through small molecule engagement of the ribosome nascent chain
Organism
Number of Samples	22
Release Date	2017/02/03 00:00
Sequencing Types
Protocol Details

Title
Authors	Lintner NG,McClure KF,Petersen D,Londregan AT,Piotrowski DW,Wei L,Xiao J,Bolt M,Loria PM,Maguire B,Geoghegan KF,Huang A,Rolph T,Liras S,Doudna JA,Dullea RG,Cate JH
Journal	PLoS biology
Publication Date	2017 Mar
Abstract	Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a key role in regulating the levels of plasma low-density lipoprotein cholesterol (LDL-C). Here, we demonstrate that the compound PF-06446846 inhibits translation of PCSK9 by inducing the ribosome to stall around codon 34, mediated by the sequence of the nascent chain within the exit tunnel. We further show that PF-06446846 reduces plasma PCSK9 and total cholesterol levels in rats following oral dosing. Using ribosome profiling, we demonstrate that PF-06446846 is highly selective for the inhibition of PCSK9 translation. The mechanism of action employed by PF-06446846 reveals a previously unexpected tunability of the human ribosome that allows small molecules to specifically block translation of individual transcripts.
PMC	PMC5360235
PMID	28323820
DOI

Lintner et al. 2017 (PRJNA369742)