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

Gopalakrishna Poornima, Gaurav Srivastava, Brinta Roy, Ishwarya Achappa Kuttanda, Iladeiti Kurbah, Purusharth I Rajyaguru

RNA biology 2021 Dec

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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/RGG-motif 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 RGG-motif protein responsible for translational repression without affecting mRNA levels.

Citation

Gopalakrishna Poornima, Gaurav Srivastava, Brinta Roy, Ishwarya Achappa Kuttanda, Iladeiti Kurbah, Purusharth I Rajyaguru. RGG-motif containing mRNA export factor Gbp2 acts as a translation repressor. RNA biology. 2021 Dec;18(12):2342-2353