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mRNA 5' terminal sequences drive 200-fold differences in expression through effects on synthesis, translation and
Antonia M G van den Elzen1, Maegan J Watson1, Carson C Thoreen1
1Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, Connecticut, United States of America.
Plos Genetics
|November 28, 2022
Summary
Investigating 5' terminal sequences in human cells revealed their significant impact on gene expression, influencing transcription, translation, and mRNA decay for distinct growth-responsive profiles.
Area of Science:
- Molecular Biology
- Gene Regulation
- Post-transcriptional Control
Background:
- mRNA regulatory sequences are crucial for controlling gene expression.
- 5' terminal sequences are particularly important due to their proximity to key regulators.
Purpose of the Study:
- To systematically investigate the function of 5' terminal sequences in gene expression in human cells.
- To identify sequence features that impact transcription, translation, and mRNA decay.
Main Methods:
- Utilized a reporter mRNA library with all possible 7-mer sequences at the 5' end.
- Analyzed transcription, translation, and decay rates for different sequences.
- Compared reporter sequences to endogenous mRNA sequences.
Main Results:
- Discovered that 5' sequences unexpectedly impact transcription, causing up to 200-fold differences in mRNA expression.
- Identified two main classes of transcription-promoting sequences similar to Inr and TCT motifs.
- Found sequences optimized for transcription, translation, and stability, including terminal oligopyrimidine (TOP) motif variants.
- Observed enrichment of multi-functional TCT/TOP hybrid sequences in endogenous mRNA 5' ends.
Conclusions:
- 5' terminal sequences play a critical role in defining gene expression profiles.
- These sequences dictate distinct, growth-responsive expression patterns across synthesis, translation, and decay.
- The findings reveal a novel layer of gene regulation mediated by 5' mRNA sequences.
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