The 5′ Leader of the mRNA Encoding the Mouse Neurotrophin Receptor TrkB Contains Two Internal Ribosomal Entry Sites that Are Differentially Regulated
2008

Two IRESes in the Mouse TrkB mRNA

publication Evidence: moderate

Author Information

Author(s): Timmerman Stephanie L., Pfingsten Jennifer S., Kieft Jeffrey S., Krushel Les A.

Primary Institution: University of Colorado Denver School of Medicine

Hypothesis

If IRES-dependent translation was a critical mechanism for the synthesis of TrkB protein, then both the presence of an IRES and its mechanism would be evolutionarily conserved.

Conclusion

The mouse TrkB mRNA contains two differentially regulated IRESes that initiate translation under specific cellular conditions.

Supporting Evidence

  • The mouse TrkB mRNA has two independent IRESes that are differentially regulated.
  • Exon 1 contains an IRES that is active in both differentiated and undifferentiated cells.
  • Exon 2 IRES activity is enhanced in differentiated cells and requires the PTB1 protein.

Takeaway

The study found that the mouse TrkB mRNA has two special regions that help it make proteins without needing a cap, and these regions work differently depending on the cell's state.

Methodology

The study used dicistronic RNA transfections and in vitro translation assays to test for IRES activity in mouse TrkB mRNA.

Limitations

The use of dicistronic constructs may lead to misinterpretation of IRES activity due to potential cryptic splicing or promoter activity.

Digital Object Identifier (DOI)

10.1371/journal.pone.0003242

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