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PLoS One. 2014 Sep 3;9(9):e104631. doi: 10.1371/journal.pone.0104631. eCollection 2014.

Grsf1-induced translation of the SNARE protein Use1 is required for expansion of the erythroid compartment.

Author information

1
Dept. Hematology, Erasmus MC, Rotterdam, The Netherlands.
2
Inst. Biochemistry, University Medicine Berlin-Charité, Berlin, Germany.
3
Dept. Hematopoiesis at Sanquin Research, and Landsteiner Laboratory AMC/UvA, Amsterdam, The Netherlands.
4
Dept. Pathology, University of Malta Medical School, Msida, Malta.
5
Dept. Hematology, Erasmus MC, Rotterdam, The Netherlands; Dept. Hematopoiesis at Sanquin Research, and Landsteiner Laboratory AMC/UvA, Amsterdam, The Netherlands.

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 5'UTR 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 5'UTR 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 5'UTR 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.

PMID:
25184340
PMCID:
PMC4153549
DOI:
10.1371/journal.pone.0104631
[Indexed for MEDLINE]
Free PMC Article

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