PLX042009

GSE134606: Polysome profiling quantified by RNA sequencing in ER knockdown and control BM67 cells

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

Estrogen receptor alpha (ER) activity is associated with increased cancer cell proliferation. Studies aiming to understand the impact of ER on cancer-associated phenotypes have largely been limited to its transcriptional activity. Herein, we demonstrate that ER coordinates its transcriptional output with selective modulation of mRNA translation. Importantly, translational perturbations caused by depletion of ER largely manifest as "translational offsetting" of the transcriptome, whereby amounts of translated mRNAs and corresponding protein levels are maintained constant despite changes in mRNA abundance. Transcripts whose levels, but not polysome-association, are reduced following ER depletion lack features which limit translation efficiency including structured 5'UTRs and miRNA target sites. In contrast, mRNAs induced upon ER depletion whose polysome-association remains unaltered are enriched in codons requiring U34-modified tRNAs for efficient decoding. Consistently, ER regulates levels of U34-modifying enzymes and thereby controls levels of U34-modified tRNAs. These findings unravel a hitherto unprecedented mechanism of ER-dependent orchestration of transcriptional and translational programs that may be a pervasive mechanism of proteome maintenance in hormone-dependent cancers. SOURCE: Ola Larsson Karolinska Institute