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Title: | Grsf1-induced translation of the SNARE protein use1 is required for expansion of the erythroid compartment |
Authors: | Nieradka, Andrzej Ufer, Christoph Thiadens, Klaske Grech, Godfrey Horos, Rastislav Coevorden-Hameete, Marleen van Akker, Emile van den Sofi, Sajad Kuhn, Hartmut Lindern, Marieke von |
Keywords: | Cell proliferation SNARE proteins Erythrocytes |
Issue Date: | 2014 |
Publisher: | PLOS |
Citation: | Nieradka, A, Ufer, C., Thiadens, K., Grech, G., Horos, R, Van Coevorden-Hameete, M.,...Von Lindern, M. (2014). Grsf1-induced translation of the SNARE protein use1 is required for expansion of the erythroid compartment. PLoS ONE, 9(9), E104631. |
Abstract: | Induction of cell proliferation requires a concomitant increase in the synthesis of glycosylated lipids and membrane proteins, which is dependent on ER-Golgi protein transport by CopII-coated vesicles. In this process, retrograde transport of ER resident proteins from the Golgi is crucial to maintain ER integrity, and allows for anterograde transport to continue. We previously showed that expression of the CopI specific SNARE protein Use1 (Unusual SNARE in the ER 1) is tightly regulated by eIF4E-dependent translation initiation of Use1 mRNA. Here we investigate the mechanism that controls Use1 mRNA translation. The 59UTR of mouse Use1 contains a 156 nt alternatively spliced intron. The non-spliced form is the predominantly translated mRNA. The alternatively spliced sequence contains G-repeats that bind the RNA-binding protein G-rich sequence binding factor 1 (Grsf1) in RNA band shift assays. The presence of these G-repeats rendered translation of reporter constructs dependent on the Grsf1 concentration. Down regulation of either Grsf1 or Use1 abrogated expansion of erythroblasts. The 59UTR of human Use1 lacks the splice donor site, but contains an additional upstream open reading frame in close proximity of the translation start site. Similar to mouse Use1, also the human 59UTR contains G-repeats in front of the start codon. In conclusion, Grsf1 controls translation of the SNARE protein Use1, possibly by positioning the 40S ribosomal subunit and associated translation factors in front of the translation start site. |
URI: | https://www.um.edu.mt/library/oar//handle/123456789/25226 |
Appears in Collections: | Scholarly Works - FacM&SPat |
Files in This Item:
File | Description | Size | Format | |
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Grsf1-induced translation of the SNARE protein Use1 is required for expansion of the erythroid compartment.pdf | 1.48 MB | Adobe PDF | View/Open |
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