Journal
NUCLEIC ACIDS RESEARCH
Volume 43, Issue 16, Pages 8077-8088Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkv748
Keywords
-
Categories
Funding
- University of Pittsburgh Dietrich School of Arts and Sciences
- Magee Womens Research Institute at the University of Pittsburgh Medical Center (MWRIF) [8059]
- CNRS
- University of Perpignan
- NSLS [DE-AC02-98CH10886]
- [NIH/NIGMS 8P41GM103473-16]
- [DOE/BER FWP BO-70]
- Wellbeing of Women [RG1319] Funding Source: researchfish
Ask authors/readers for more resources
La-related protein 1 (LARP1) regulates the stability of many mRNAs. These include 5'TOPs, mTOR-kinase responsive mRNAs with pyrimidine-rich 5' UTRs, which encode ribosomal proteins and translation factors. We determined that the highly conserved LARP1-specific C-terminal DM15 region of human LARP1 directly binds a 5'TOP sequence. The crystal structure of this DM15 region refined to 1.86 angstrom resolution has three structurally related and evolutionarily conserved helix-turn-helix modules within each monomer. These motifs resemble HEAT repeats, ubiquitous helical protein-binding structures, but their sequences are inconsistent with consensus sequences of known HEAT modules, suggesting this structure has been repurposed for RNA interactions. A putative mTORC1-recognition sequence sits within a flexible loop C-terminal to these repeats. We also present modelling of pyrimidine-rich single-stranded RNA onto the highly conserved surface of the DM15 region. These studies lay the foundation necessary for proceeding toward a structural mechanism by which LARP1 links mTOR signalling to ribosome biogenesis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available