Translational control of cancer and stromal cells – Dr. Ola Larsson
Abstract
Estrogen receptor alpha (ERα) activity is associated with increased cancer cell proliferation. Studies aiming to understand the impact of ERα on cancer-associated phenotypes have largely been limited to its transcriptional activity. Herein, we demonstrate that ERα coordinates its transcriptional output with selective modulation of mRNA translation. Importantly, translational perturbations caused by depletion of ERα 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 ERα depletion lack features which limit translation efficiency including structured 5’UTRs and miRNA target sites. In contrast, mRNAs induced upon ERα depletion whose polysome association remains unaltered are enriched in codons requiring U34-modified tRNAs for efficient decoding. Consistently, ERα regulates levels of U34-modifying enzymes and thereby controls levels of U34-modified tRNAs. These findings unravel a hitherto unprecedented mechanism of ERα-dependent orchestration of transcriptional and translational programs that may be a pervasive mechanism of proteome maintenance in hormone-dependent cancers.
Date: 09/04/2021 – 17.00 GMT+3
Ola Larsson is an associate professor at the Department of Oncology-Pathology in Karolinska Institutet and SciLifeLab, Sweden. He obtained his Ph.D. in Functional Genomics from Karolinska Institutet and he has completed his postdoctoral studies on translational control of cancer at the University of Minnesota and mechanisms of translational control at McGill University between 2005-2010. By combining biomedicine, statistics, and informatics, Ola Larsson is mapping the regulation of protein production in cancer cells. His aim is to gain a fundamental understanding of why cancer cell growth is uncontrolled. It is hoped that it will be possible in the future to use drugs to restore order in cancer cells.
A tutorial: Transcriptome wide analysis of translational efficiency – İnci Şevval Aksoylu (PhD Student)
Date: 09/04/2021 – 18.00 GMT+3
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