YB-1, an abundant core mRNA-binding protein, has the capacity to form an RNA nucleoprotein filament: a structural analysis.

 The SABNP lab  recently provides new insights into the remodeling of the mRNA during translation. In a collaborative project, we found that YB-1, an abundant cytoplasmic mRNA-binding protein, unfolds mRNA into a nucleoprotein filament.

This is the first time that the formation of a linear nucleoprotein filament with mRNA is revealed. The stretched conformation may facilitate the reading of mRNA for protein synthesis. This study, published in the journal Nucleic Acids Research of January 3, 2019, paves the way for new discoveries on translation regulation, with putative application in the field of cancer.

To reach these conclusions, the SABNP lab, in collaboration with Russian researchers (Pr Lev Ovchinnikov, Institute of Protein Research, Russian Academy of Sciences in Pushchino) led for three years a thorough study on the structure of the YB-1:RNA complex. In addition, the spin-off of the laboratory, Synsight, participated in molecular dynamics analysis.

YB-1 is one of the major proteins associated with mRNA in the cytoplasm. It is also known for its role in cancer: YB-1 is found at high concentrations in various cancers, for which it promotes high proliferation rates and expression of oncogenes.

In vitro, full length YB-1 packages the mRNA. But when part of its unstructured C-terminus is truncated, it leads on the contrary to the formation of an extended mRNA filament. Interestingly, the translation of mRNA is preserved under in vitro conditions, when the filament is formed.

Using NMR spectroscopy, we show that the remodeling of mRNA into a linear filament is orchestrated by the “cold shock”, a domain present in YB-1. It is inherited from bacterial proteins, the “cold shock” proteins, which are overexpressed at low temperatures to allow translation to take place by unwinding strong secondary structures.

This discovery paves the way for new research in cell biology, notably to clarify the role of mRNA filaments or understand how this phenomenon is regulated in the cell.

Given the known link between YB-1 and several cancers, this work offers interesting perspectives to propose novel strategies to treat cancers.

2019 Jan 3. doi: 10.1093/nar/gky1303. [Epub ahead of print]