Life Sciences & Biotechnology
Title : | Identification and characterization of modulators of RGG-motif containing translation repressor Scd6 |
Area of research : | Life Sciences & Biotechnology |
Focus area : | Translational Regulation |
Principal Investigator : | Dr. Purusharth I Rajyaguru, Indian Institute Of Science, Bangalore, Karnataka |
Timeline Start Year : | 2023 |
Timeline End Year : | 2026 |
Contact info : | rajyaguru@biochem.iisc.ernet.in |
Details
Executive Summary : | RNA-binding proteins play a crucial role in controlling gene expression by regulating translation and mRNA decay. RGG-motif proteins, characterized by arginine and glycine repeats, affect various cellular processes, including transcription, splicing, mRNA export, translation, and decay. Scd6 and its ortholog proteins are a key family of RGG-motif proteins involved in cytoplasmic mRNA fate regulation. Scd6 is a modular protein with an N-terminal Lsm domain, a central FDF domain, and a C-terminal RGG-motif. It represses translation in a RGG-motif dependent manner by targeting eIF4G and affecting the formation of 48S pre-initiation complex. Arginine methylation of Scd6 RGG-motif promotes repression activity by augmenting interaction with eIF4G1. Self-association of Scd6 via its RGG-motif competes with eIF4G1 interaction, and arginine methylation inhibits self-interaction. Other domains of Scd6, such as Lsm, also contribute to its role in translation repression. Few transcripts have been identified as direct targets of Scd6 using polysome profiling analysis. LSM14, a human homolog of Scd6, localizes to RNA granules and undergoes arginine methylation. It is also part of RNA silencing complexes. Scd6 proteins belong to a conserved family that plays an important role in determining mRNA fate. The proposal aims to identify proteins and pathways that modulate Scd6 activity in determining mRNA fate, hypothesizing that specific protein factors would directly or indirectly contribute towards modulating Scd6 activity under specific physiological conditions. |
Total Budget (INR): | 69,93,888 |
Organizations involved