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Global Analysis of the of the Human RNA Degradome

The control of gene expression is fundamental to all phases of growth and development, and gene expression changes that affect the abundance of specific mRNAs have been associated with numerous human diseases. These changes are most often attributed to transcriptional control, especially when monitored from a genomic perspective. However, RNA decay can have a great influence on mRNA levels, and most transcriptome profiling techniques do not consider this component or represent a composite of transcriptional activity and RNA decay. By profiling the RNA degradome with an approach called PARE (Parallel Analysis of RNA Ends), this project examines millions of heterogeneous degradation products of human mRNAs and noncoding RNAs genome-wide. A comparison of PARE data from different samples should reveal new gene regulatory mechanisms, potential disease associations, and aid in the interpretation of transcriptome data. The PARE Explorer is powered by J2EE and MySQL technologies to allow examination of the RNA decay profiles for any annotated gene or genomic region in the human genome.

Each of the RNAs made from the human genome can be degraded by one or more cellular ribonucleases, some of which cut the RNA internally, while others degrade RNA from the ends. In this project, PARE libraries are made that capture the 5' ends of partially degraded molecules from each sample. Millions of sequences are read to determine from which RNA and corresponding gene each of the molecules derive. The degradation pattern for the RNA from each gene in the human genome is then determined by plotting the data as shown. These RNA decay profiles, or D-plots, are then compared within a sample and among different samples to gain new insights about regulation and mechanisms of RNA decay that go beyond what is possible by examining individual genes.

This work is supported by NIH Transformative R0-1 GM96471
PI: Pamela J. Green, University of Delaware