What is it about?

RNA and DNA molecules have been found floating freely (outside of cells) in most human biofluids. These cell free RNA and DNA molecules have become an exciting source of information researchers have been exploring for use as non-invasive markers of human disease. This study shows that an easily-adaptable modification to a standard RNA profiling technology enables capture of large populations of RNAs that are completely missed by the standard protocols. Importantly, among these newly-discovered RNAs are small fragments of mRNA transcripts, which are shown to originate from multiple different organs and tissues, and show dynamic changes in expression in disease settings.

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Why is it important?

This study shows that successful profiling of mRNA and lncRNA molecules in biofluids requires both a modification to standard molecular methodolgy and, crucially, a highly-stringent analytical pipeline. With this framework, mRNA and lncRNA fragments can become a viable source of potential biomarkers in human health and disease.

Perspectives

Working on this study highlighted the importance of carefully scrutinizing the findings, especially when the data show you exactly what you're looking for. This study was undertaken in the hope that we would find evidence of mRNA and lncRNA fragments in plasma, and initial mapping and analysis of gene expression using standard bioinformatics workflows showed extensive, abundant expression of hundreds of genes. However, careful study of the alignments showed that most of these alignments were false-positives, resulting from bacterial, viral and genomic "contaminates" present in the sequencing data. This led us to develop a more stringent pipeline that identifies and separates out these problematic sequences. I was extremely excited to find that after all this filtering, there remained a clear signal in mRNA and lncRNA exons.

Ryan M Spengler
University of Michigan

Read the Original

This page is a summary of: Phospho‐RNA‐seq: a modified small RNA‐seq method that reveals circulating mRNA and lncRNA fragments as potential biomarkers in human plasma, The EMBO Journal, May 2019, EMBO, DOI: 10.15252/embj.2019101695.
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