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Exploring Sequence Space to Identify Binding Sites for Regulatory RNA-Binding Proteins
Published on: August 9, 2019
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YB-3 substitutes YB-1 in global mRNA binding.
D N Lyabin1, I A Eliseeva1, E A Smolin1
1Institute of Protein Research, Russian Academy of Sciences, Pushchino, Russia.
RNA Biology
|January 17, 2020
Summary
Y-box binding protein 1 (YB-1) inhibits translation of many mRNAs. In YB-1-null cells, YB-3 compensates by binding mRNAs and inhibiting their translation, suggesting YB-3 acts as a YB-1 substitute.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- Y-box binding proteins (YBPs) are ancient DNA/RNA-binding proteins.
- Y-box binding protein 1 (YB-1) is abundant in somatic cells and regulates proliferation, differentiation, and stress response.
- YB-1 is known to bind mRNAs and influence translation.
Purpose of the Study:
- To investigate the global impact of YB-1 on mRNA binding and translation.
- To elucidate the role of YB-3 in the absence of YB-1.
- To understand the functional relationship between YB-1 and YB-3 in translational control.
Main Methods:
- Ribosome profiling (Ribo-Seq) to analyze translation.
- RNA immunoprecipitation sequencing (RIP-Seq) to identify bound mRNAs.
- Gene knockout studies (YBX1 knockout) to assess YB-1's function.
Main Results:
- YB-1 binds numerous mRNAs and globally inhibits their translation.
- YBX1 knockout causes minor gene expression changes, primarily due to altered RNA abundance.
- YB-3 mRNA translation is enhanced in YB-1-null cells, indicating negative regulation by YB-1.
- YB-3 binds a similar set of mRNAs as YB-1, and its binding is enhanced in YB-1-null cells.
- YB-3 binding leads to global translation reduction of bound mRNAs in YB-1-null cells.
Conclusions:
- YB-1 globally inhibits translation of a wide range of mRNAs.
- YB-3 can substitute for YB-1 in mRNA binding and global translational control.
- YB-3 synthesis is under negative control by YB-1.
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