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Open Access Publications from the University of California

Identifying the determinants for IRES-mediated translation of a voltage-gated potassium channel mRNA

  • Author(s): Baggs, Eric
  • Advisor(s): Semler, Bert L
  • et al.
No data is associated with this publication.

Internal ribosome entry sites (IRESs) are regions of mRNA that facilitate direct binding of components of the initiation complex for protein synthesis independent of the 5’-terminus. While first discovered in viruses, there are many cellular mRNAs that harbor these elements. The current study is evaluating the requirements (both canonical and non-canonical) for translation initiation on the voltage-gated potassium-channel (Kv1.4) IRES. Kv1.4 is a shaker related family member which contributes to the repolarizing phase of the cardiac action potential. Kv1.4 has a highly tissue-specific expression, despite its relatively non-specific promoter, and is regulated at the post-transcriptional level. Using both a genetic (yeast 3-hybrid screen) and a biochemical approach (biotinylated-RNA capture), we probed for novel interacting proteins that might modulate the activity of these IRES elements. Parallel screens reveal a diversity of interacting proteins, which may represent trans-acting factors for translation initiation. Gene set enrichment analysis as well as manual cross-reference identify a high abundance of RNA and translation associated proteins with and without ascribed functions in IRES-mediated translation. Characterizations of a select group of these interactions indicate roles in translation initiation and allude to tissue specific mechanisms of post-transcriptional regulation.

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This item is under embargo until December 14, 2019.