RGG-motif containing mRNA export factor Gbp2 acts as a translation repressor

Abstract

Complex cascades of RNA-binding proteins regulate the mRNA metabolism and influence gene expression. Several distinct proteins act at different stages of mRNA life cycle. SR family proteins in yeast are implicated in mRNA processing and nuclear export. In this report, we uncover the role of an SR/RGGmotif containing mRNA export factor Gbp2 in mRNA translation regulation. We demonstrate that Gbp2 localizes to cytoplasmic granules upon heat shock and oxidative stress. Our pull-down assays demonstrate that Gbp2 directly binds to the conserved translation factor eIF4G1 via its RGG motif. We further mapped the region on eIF4G1 to which Gbp2 binds and observed that the binding region overlaps with another translation repressor Sbp1. We found that the RGG-motif deletion mutant is defective in localizing to polysome fractions. Upon tethering Gbp2 to a GFP reporter mRNA in vivo, translation of GFP reporter decreased significantly indicating that Gbp2 acts as a translation repressor. Consistent with these results, we show that Gbp2 can directly repress mRNA translation in the in vitro translation systems in an RGG-motif dependent manner. Taken together, our results establish that the mRNA export factor Gbp2 has a vital role in repressing translation of mRNA. We propose that Gbp2 is a multifaceted RGGmotif protein responsible for translational repression without affecting mRNA levels.

Cold‐inducible RNA‐binding protein regulates cyclin B1 against spermatogenesis arrest caused by heat stress

“…21 Heat stress also leads to the extensive reprogramming of mRNA processing, export, and translation, with concomitant formation of RNA granules in the cytoplasm. 22 The GO enrichment analysis in this study showed that DEmRNAs are mainly involved in biological processes such as cell cycle regulation, spermatogenesis, and transcriptional regulation, suggesting that CIRBP may influence spermatogenesis by participating in these processes. In addition, CIRBP has been shown to be associated with the cell cycle and spermatogenic functions.…”

“…Intracellularly, endoplasmic reticulum stress can be induced by heat stress, and a reduction in CIRBP expression after heat stress may induce this stress by leading to the accumulation of misfolded proteins in the endoplasmic reticulum 21 . Heat stress also leads to the extensive reprogramming of mRNA processing, export, and translation, with concomitant formation of RNA granules in the cytoplasm 22 . The GO enrichment analysis in this study showed that DEmRNAs are mainly involved in biological processes such as cell cycle regulation, spermatogenesis, and transcriptional regulation, suggesting that CIRBP may influence spermatogenesis by participating in these processes.…”

Nuclear mRNA Quality Control and Cytoplasmic NMD Are Linked by the Guard Proteins Gbp2 and Hrb1

“…Besides RNA degradation, Gbp2 and Hrb1 may also serve specific functions in translation repression in NMD. Recent studies demonstrated that Gbp2 and Hrb1 show features similar to a group of yeast RGG motif-containing proteins that act as translation repressors [104,134]. These proteins inhibit translation initiation through their RGG motifdependent interaction with eIF4G, a scaffold protein of the cap-binding eIF4F complex important for eukaryotic translation initiation (reviewed in [128]).…”

“…Recently, it was shown that SRSF1 stimulates NMD by promoting Upf1 binding, and that SRSF2 affects the association of key NMD factors [137,138], demonstrating more direct links between SR proteins and cytoplasmic surveillance. Apart from NMD, Gbp2 can act as a translation repressor [134], whereas some SR proteins were shown to either suppress or enhance the translation of specific mRNAs [139,140]. An additional correlation is provided by the discovery of homologous proteins that phosphorylate these proteins-the yeast kinase Sky1 and its mammalian counterpart SRPK1 [141]-and mediate their import-the import receptors Mtr10 (in yeast) and TRN-SR (in Mammalia), respectively [142].…”

“…The family of SR proteins plays critical roles in splicing, but the range of their cellular activities is still expanding. For example, Gbp2 and several human SR proteins were found to accumulate in stress granules or distinct cytoplasmic foci under specific types of cellular stress, and were suggested to participate in translation repression under these circumstances [134,148,149]. In addition, transcriptome-wide analysis of yeast RNPs has revealed that Gbp2 is also strongly associated with small nucleolar RNAs and long noncoding (lnc) RNAs [117].…”