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. 2019 Jan 17;2(1):e201800131. doi: 10.26508/lsa.201800131

Figure 7. Model for the IRES role in RNA localization on the ER-Golgi compartment.

Figure 7.

Interaction of the IRES through its central domain (D3) with Rab1b (orange circles) enables mRNA localization on the ER (solid line). In addition to initiation factors (eIFs) and IRES-transacting factors (ITAFs) (brown, red, blue, and pink circles) depicted in the center of the image (solid line), the interaction of the IRES with Rab1b within the cell cytoplasm guides the mRNA to the ER, activating IRES-dependent translation. This hypothesis is consistent with the ER localization of reporter RNAs carrying the EMCV IRES (Lerner & Nicchitta, 2006), a picornavirus IRES similar to FMDV (Lozano & Martinez-Salas, 2015). This pathway may occur concomitantly to eIFs- and IRES-transacting factors–mediated translation (Martinez-Salas et al, 2015; Lee et al, 2017). Colocalization of Rab1b on the ER membranes depends upon the GTP status of Rab1b (Alvarez et al, 2003; Hutagalung & Novick, 2011). Thus, the dominant-negative Rab1b DN (orange squares), unable to exchange GTP and blocking ER-Golgi trafficking (Alvarez et al, 2003; Midgley et al, 2013), impairs ER-RNA juxtapositioning (dashed line), thereby RNA translation. Interaction of the IRES with ARF5 (green circles) sequesters the mRNA on the trans-Golgi (dashed line), presumably interfering IRES-driven translation.