Arginine methylation promotes translation repression activity of eIF4G-binding protein, Scd6.
Regulation of translation plays a critical role in determining mRNA fate. A new role was recently reported for a subset of RGG-motif proteins in repressing translation initiation by binding eIF4G1. However the signaling mechanism(s) that leads to spatial and temporal regulation of repression activity of RGG-motif proteins remains unknown. Here we report the role of arginine methylation in regulation of repression activity of Scd6, a conserved RGG-motif protein. We demonstrate that Scd6 gets arginine methylated at its RGG-motif and Hmt1 plays an important role in its methylation. We identify specific methylated arginine residues in the Scd6 RGG-motif in vivo We provide evidence that methylation augments Scd6 repression activity. Arginine methylation defective (AMD) mutant of Scd6 rescues the growth defect caused by overexpression of Scd6, a feature of translation repressors in general. Live-cell imaging of the AMD mutant revealed that it is defective in inducing formation of stress granules. Live-cell imaging and pull-down results indicate that it fails to bind eIF4G1 efficiently. Consistent with these results, a strain lacking Hmt1 is also defective in Scd6-eIF4G1 interaction. Our results establish that arginine methylation augments Scd6 repression activity by promoting eIF4G1-binding. We propose that arginine methylation of translation repressors with RGG-motif could be a general modulator of their repression activity.
Department of Biochemistry, Indian Institute of Science, C V Raman Road, Bangalore 560012, India.
Gopalakrishna
G
Poornima
Department of Biochemistry, Indian Institute of Science, C V Raman Road, Bangalore 560012, India.
Shanaya
S
Shah
Department of Biochemistry, Indian Institute of Science, C V Raman Road, Bangalore 560012, India.
Venkadasubramanian
V
Vignesh
Department of Chemistry and Biochemistry, University of Colorado, 596 UCB, Boulder, CO 80309, USA.
Roy
R
Parker
Department of Biochemistry, Indian Institute of Science, C V Raman Road, Bangalore 560012, India rajyaguru@biochem.iisc.ernet.in.
Purusharth I
PI
Rajyaguru
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001120:Arginine / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D008745:Methylation; D009154:Mutation; D011485:Protein Binding; D014176:Protein Biosynthesis; D016601:RNA-Binding Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D005656:Fungal Proteins; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D001120:Arginine