3m93

Publication Abstract from PubMed

Metazoan spliced leader (SL) trans-splicing generates mRNAs with an m(2,2,7)G-cap and a common downstream SL RNA sequence. The mechanism for eIF4E binding an m(2,2,7)G-cap is unknown. Here, we describe the first structure of an eIF4E with an m(2,2,7)G-cap and compare it to the cognate m(7)G-eIF4E complex. These structures and Nuclear Magnetic Resonance (NMR) data indicate that the nematode Ascaris suum eIF4E binds the two different caps in a similar manner except for the loss of a single hydrogen bond on binding the m(2,2,7)G-cap. Nematode and mammalian eIF4E both have a low affinity for m(2,2,7)G-cap compared with the m(7)G-cap. Nematode eIF4E binding to the m(7)G-cap, m(2,2,7)G-cap and the m(2,2,7)G-SL 22-nt RNA leads to distinct eIF4E conformational changes. Additional interactions occur between Ascaris eIF4E and the SL on binding the m(2,2,7)G-SL. We propose interactions between Ascaris eIF4E and the SL impact eIF4G and contribute to translation initiation, whereas these interactions do not occur when only the m(2,2,7)G-cap is present. These data have implications for the contribution of 5'-UTRs in mRNA translation and the function of different eIF4E isoforms.

Structural basis for nematode eIF4E binding an m2,2,7G-Cap and its implications for translation initiation.,Liu W, Jankowska-Anyszka M, Piecyk K, Dickson L, Wallace A, Niedzwiecka A, Stepinski J, Stolarski R, Darzynkiewicz E, Kieft J, Zhao R, Jones DN, Davis RE Nucleic Acids Res. 2011 Sep 29. PMID:21965542^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.