The molecular structural basis of TIA-1 central domains binding to novel C-rich RNA sequence. — ASN Events
  1. Schedule
  2. Session 5: Poster Session A
  3. The molecular structural basis of TIA-1 central domains binding to novel C-rich RNA sequence.

The molecular structural basis of TIA-1 central domains binding to novel C-rich RNA sequence. (#187)

Saboora Waris 1 , Andrew Sivakumaran 1 , Simone Beckham 1 , Isabel Cruz-Gallardo 2 , Irene Diaz Moreno 2 , Matthew Wilce 1 , Jackie Wilce 1
  1. Department of Biochemisty and Molecular biology, School of Biomedical sciences, Monash University, Australia, Victoria, VIC 3800, Australia
  2. Instituto de Bioquímica Vegetal y Fotosíntesis, Centro de Investigaciones Científicas Isla de la Cartuja, Universidad de Sevilla-CSIC, Sevilla, Spain

The fate of mRNA once transcribed, spliced and transported to the cytoplasm is determined by the intricate interplay between RNA binding proteins (RBPs) and microRNAs (miRNAS), that interact with regulatory elements on mRNA. T-cell intracellular antigen-1 (TIA-1) is DNA/RNA binding protein that shuttles between the nucleus and the cytoplasm to regulate at both transcriptional and post-transcriptional levels. Post-transcriptional regulation is achieved by sequestration of mRNA into stress granules under conditions of cellular stress. TIA-1 first binds A/U-rich elements in 3’UTR regions of mRNAs, and then escorts the translational initiation complex into stress granules repressing the process of translation.

TIA-1 possesses three RNA recognition motifs RRM1, RRM2, RRM3 and a Q-rich domain. Among the domains, RRM2 is the major RNA recognition domain for U and A/U-rich sequences. We have recently determined that RRM3 confers additional sequence specificity for a novel C-rich RNA motif, as shown by Surface Plasmon Resonance (SPR) experiments in our lab. This study aims to determine the detailed molecular structural basis of this specificity of RRM3 to C- rich sequences (using both SAXS and X-ray crystallography). This will elucidate the role of RRM3 in regulating TIA-1 binding to C-rich motifs that are numerous at the 5’ TOPs (5’ Terminal Oligopyrimidine Tracts) of mRNAs whose translation is repressed under stress conditions.