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Updated: May 5, 2026
12:49
Mutagenesis and Analysis of Genetic Mutations in the GC-rich KISS1 Receptor Sequence Identified in Humans with Reproductive Disorders
Published on: September 4, 2011
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Structure-informed mutagenesis identifies a conserved region critical for mouse insulin receptor 5'UTR IRES function
Biorxiv : the Preprint Server for Biology
|November 22, 2024
Summary
Cells use internal ribosome entry sites (IRES) for translation during stress. Researchers mapped the insulin receptor 5' untranslated region (Insr 5'UTR) structure, identifying a key region for cap-independent translation.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- Cells repress cap-dependent translation during stress.
- Internal ribosome entry sites (IRES) enable translation of key transcripts under stress.
- The RNA secondary structures of cellular IRESes are largely unknown.
Purpose of the Study:
- To probe the secondary structure of the insulin receptor 5' untranslated region (Insr 5'UTR) IRES in cells.
- To identify structural elements critical for Insr IRES function.
- To design a minimal IRES element with high cap-independent translation activity.
Main Methods:
- Dimethyl sulfate mutational profiling by sequencing (DMS-MaPseq) was used to probe RNA secondary structure in vitro and in cells.
- A mutation strategy was employed, guided by a structural model of the Insr 5'UTR.
- Viral IRESes (HCV, EMCV) were used as controls.
Main Results:
- Viral IRES structures in cells were consistent with known in vitro structures.
- Significant linearization of viral IRESes occurred near the translation start codon in cells.
- A conserved segment of the Insr 5'UTR, distal to the start codon, was identified as critical for IRES activity.
Conclusions:
- A structural model of the Insr 5'UTR was generated using DMS-MaPseq data.
- A minimal Insr IRES element with full activity was designed.
- This work elucidates cellular IRES structure and function, aiding stress response research.
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