Genome-wide analysis of RNA-protein interactions illustrates specificity of the mRNA export machinery
Haley Hieronymus1, Pamela A Silver
1Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School and the Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Abstract:
Nuclear export of mRNA is mediated by a complex machinery of RNA-binding proteins that recognizes and routes mRNAs through a messenger ribonucleoprotein (mRNP) network. The full spectrum of mRNA cargoes for any dedicated mRNA export factor is unknown. We identified the mRNAs that bind two conserved yeast mRNA export factors, Yra1 (refs. 1-5) and Mex67 (refs. 6,7), on a genome-wide scale and determined their level of binding. Yra1 and Mex67 bind approximately 1,000 and 1,150 mRNAs, respectively, corresponding to almost 20% of the yeast genome and roughly 36% of all transcriptional events each. The binding level of Yra1 targets is related to their transcriptional frequency, but that of Mex67 targets is not. Yra1-bound transcripts are enriched in mRNAs that are regulated by a number of transcription factors. Yra1- and Mex67-bound populations also show enrichment of mRNAs encoding distinct functional classes of proteins, some of which are regulated by these transcription factors. We determined that one such transcription factor, Abf1 (refs. 8-10), associates with Yra1. These results indicate a previously unidentified specificity of mRNA export factors, which coordinates the export of transcriptionally co-regulated, functional classes of transcripts, perhaps through interactions with the transcriptional machinery.
Insights
Researchers identified specific messenger RNA (mRNA) export factors, Yra1 and Mex67, binding nearly 20% of yeast genes. This reveals a coordinated export process for co-regulated functional mRNA transcripts.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- Nuclear export of messenger RNA (mRNA) relies on RNA-binding proteins forming a messenger ribonucleoprotein (mRNP) network.
- The complete set of mRNA targets for specific export factors remains largely uncharacterized.
Purpose of the Study:
- To identify, on a genome-wide scale, the specific mRNAs bound by two conserved yeast mRNA export factors, Yra1 and Mex67.
- To determine the binding levels and functional relevance of these mRNA-export factor interactions.
Main Methods:
- Genome-wide identification of mRNA targets for Yra1 and Mex67 in yeast.
- Analysis of the relationship between mRNA binding levels, transcriptional frequency, and functional classes of proteins encoded by the bound mRNAs.
- Investigation of potential interactions between mRNA export factors and transcription factors.
Main Results:
- Yra1 and Mex67 bind approximately 1,000 and 1,150 different mRNAs, respectively, representing about 20% of the yeast genome.
- Yra1 binding correlates with transcriptional frequency, while Mex67 binding does not.
- Yra1-bound transcripts are enriched for mRNAs regulated by specific transcription factors, including Abf1, and encode distinct functional protein classes.
Conclusions:
- mRNA export factors exhibit previously unrecognized specificity in binding distinct mRNA populations.
- These factors coordinate the export of transcriptionally co-regulated, functionally related mRNA classes.
- Potential interactions with the transcriptional machinery may mediate this coordination.
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