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11 Jul 2012
Paper published in the journal Molecular Cell using Human Proteome Folding project results
Category: Human Proteome Folding
A paper was published in the journal Molecular Cell, which used results from the Human Proteome Folding project in identifying proteins which regulate processes in human cells.
“The mRNA-Bound Proteome and its Global Occupancy Profile on Protein-Coding Transcripts”
Lay Person Abstract:
The Bonneau lab at NYU collaborated with Markus Landthaler and colleagues from the Max Delbruch Center for Molecular Medicine, Berlin, contributing in an effort to discover and study novel RNA-binding proteins in the human proteome. These proteins play an important role in regulating activity in the cell. Some of the proteins have been implicated in diseases such as Alzheimer’s, muscular diseases, cancers and others. This information should help scientists in further understanding of disease processes, possibly leading to better treatments.
The Landthaler group at the MDC put together a landmark experiment for discovering RNA-binding proteins - a type of protein extremely important to human genetic systems. They then contacted the Bonneau lab for computational analysis. World Community Grid has provided predicted structures for a more complete structural landscape, contributing greatly to the analysis of human protein structure and function. This analysis allowed the Bonneau lab to verify experiment results from the Landthaler lab, lending confidence to their methods and providing data on RNA-binding proteins found via experimental methods. Furthermore, cutting-edge function prediction methods were developed and proved in this experiment, which will feature World Community Grid data in future publications.
Protein-RNA interactions are fundamental to core biological processes, such as mRNA splicing, localization, degradation, and translation. We developed a photoreactive nucleotide-enhanced UV crosslinking and oligo(dT) purification approach to identify the mRNA-bound proteome using quantitative proteomics and to display the protein occupancy on mRNA transcripts by next-generation sequencing. Application to a human embryonic kidney cell line identified close to 800 proteins. To our knowledge, nearly one-third were not previously annotated as RNA binding, and about 15% were not predictable by computational methods to interact with RNA. Protein occupancy profiling provides a transcriptome-wide catalog of potential cis-regulatory regions on mammalian mRNAs and showed that large stretches in 3′ UTRs can be contacted by the mRNA-bound proteome, with numerous putative binding sites in regions harboring disease-associated nucleotide polymorphisms. Our observations indicate the presence of a large number of mRNA binders with diverse molecular functions participating in combinatorial posttranscriptional gene-expression networks.
Access to Paper:
To view the paper, please click here.