Year: 2018
Type: dissertation
Abstract: Proper control of mRNA stability is key in the regulation of gene expression, with half-lives varying considerably transcriptome-wide. While sequence elements regulating mRNA decay are classically attributed to the untranslated regions (UTRs) of the transcript, recent work across a range of non-human model systems has uncovered a conserved decay mechanism triggered by codon usage within the coding sequence (CDS). Here, I use the human ORFeome (hORFeome) collection, a library of human CDSs flanked by universal synthetic UTRs, to demonstrate that hORF constructs with different CDSs possess a wide range of stability comparable to that of endogenous transcripts. This CDS-mediated diversity in mRNA decay requires translation. I further identify codon and amino acid usage to be key elements driving this variation in stability and outline their relative impacts in yeast and humans. Overall, the hORFeome collection represents a powerful framework for deconvoluting the effects of CDSs and UTRs on stability transcriptome-wide.
Source: TSpace (University of Toronto)
Author: Ashrut Narula
Language: English
Topic: RNA Research and Splicing
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funder: Hospital for Sick Children
OpenAlex ID: W3165982044