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A possible mechanism for the regulation of IRES‐mediated expression by eIF2A
Author(s) -
Merrick William C.,
Reineke Lucas C.,
Cao Yu,
Baus Diane
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.467.5
Subject(s) - internal ribosome entry site , ribosome , biology , translation (biology) , computational biology , microbiology and biotechnology , messenger rna , genetics , gene , rna
We have shown that eIF2A has the capability of repressing expression from the URE2 IRES in vivo . 1 Current studies are addressing how this down regulation might be achieved. There are now five pieces of evidence that allow for the postulation of a model for this regulation:the eIF2A mRNA disappears within 2–3 minutes with essentially any stress eIF2A protein may or may not show enhanced degradation depending on the stress eEF1A binds to the URE2 IRES element by pull down experiments, eEF1A and eIF2A reciprocally bind each other it appears that the interaction between eEF1A and eIF2A is through the C‐terminal regions of each proteinIn the model to be presented, it is anticipated that the binding of eEF1A to the URE2 IRES‐element facilitates the binding of eIF2A (and Met‐tRNA) and that the resulting complex at the level of the 80S ribosome is slow to convert to an elongating ribosome. With the down‐regulation of eIF2A protein and/or activity, eIF2 is presumed to direct Met‐tRNA binding in a more efficient manner allowing for a 10‐fold increase in expression. Preliminary evidence indicates that the regulation of IRES‐mediated expression is not exclusive to the URE2 IRES element but that eIF2A down‐regulates expression from several other IRES elements as well (identified by Gilbert et al. 2 ).