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Virus-Induced Changes in mRNA Secondary Structure Uncover cis-Regulatory Elements that Directly Control Gene
Orel Mizrahi1, Aharon Nachshon1, Alina Shitrit1
1Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.
Molecular Cell
|October 16, 2018
Summary
Mapping dynamic mRNA structures reveals regulatory elements controlling gene expression. This method identifies cis-elements in 3' untranslated regions and coding sequences, impacting mRNA stability and translation efficiency.
Area of Science:
- Molecular Biology
- Genomics
- Bioinformatics
Background:
- Messenger RNAs (mRNAs) contain genetic code and regulatory information for post-transcriptional control.
- Identifying cis-elements and trans-regulators that govern mRNA fate is complex and challenging.
- Understanding mRNA structure dynamics is crucial for deciphering gene expression regulation.
Purpose of the Study:
- To develop an unbiased method for identifying cis-elements controlling gene expression.
- To map dynamic changes in mRNA secondary structure, particularly during viral infection.
- To investigate the relationship between mRNA structure, ribosome activity, and translation efficiency.
Main Methods:
- Utilized dimethyl sulfate (DMS) mutational profiling with sequencing (DMS-seq) to map mRNA secondary structures.
- Analyzed dynamic structural changes in viral and cellular mRNAs.
- Correlated structural data with translation efficiency and mRNA stability.
Main Results:
- Identified a significant role for ribosomes in unwinding mRNA secondary structures.
- Revealed a link between mRNA structure and translation efficiency.
- Discovered numerous regions with altered mRNA secondary structures during viral infection.
- Uncovered cis-elements in 3' UTRs affecting mRNA stability and elements in coding sequences influencing translation.
Conclusions:
- Mapping dynamic mRNA structural changes provides an unbiased approach to identify functional regulatory elements.
- This method enhances understanding of post-transcriptional gene regulation.
- The findings offer new insights into mRNA structure-function relationships and viral-host interactions.
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