MicroRNAs (miRs) are endogenously expressed small RNAs (~22-nt in length) that control the expression of protein-coding genes. These noncoding RNAs were first described and functionally examined by Victor Ambros and colleagues in 1993 (article here) using the model organism C. elegans while exploring the developmental phenotype associated with the lin-4 gene, which was found to encode a miR. In follow-up studies, early miR researchers determined that both miRs and their processing machinery are not only present in the round worm but highly conserved across species. Since that time, miRs have been an exciting area of research for the broader scientific community. The importance and function of miR regulatory networks have been established and explored in a wide variety of organisms, tissues, cells and physiological conditions. A major focus of miR research relates to their suspected roles in disease, including cardiovascular conditions; however, progress in the field is hindered by our limited knowledge of which genes are regulated by specific miRs. A given cell expresses hundreds of unique miRs and thousands of potential target protein-coding transcripts, creating a complex puzzle that remains largely unsolved. In the December edition of ACRC paper of the month, we highlight the recent work of Dr. Ryan Boudreau’s group published in the journal Nucleic Acid Research, which furthers our understanding of miR functions by describing ”the first detailed, transcriptome-wide map of miR binding sites in human cardiac tissues”. Boudreau’s group, in the collaboration with University of Pennsylvania researchers, used a state-of-the-art, high-throughput biochemical approach to identify 4000 miR binding sites across >2200 genes expressed in failing human hearts. Dr. Boudreau states that “the research in this article provides an important resource to the many scientists working on translational miR research, particularly as it relates to cardiac function and disease, and supports future efforts to interrogate how the miR-target regulatory axis is remodeled in heart failure.” Of particular note, Dr. Boudreau’s group has already explored the new dataset and subsequently found exciting and novel miR:mRNA interactions which interface with polymorphisms linked to heart disease. We hope you explore the full content of article and are welcome to provide comments and thoughts with our community below. Any questions about the article and/or collaborative ideas can be directed to Dr. Boudreau directly.
Roy J. Lucille A. Carver College of Medicine, Department of Internal Medicine, Abboud Cardiovascular Research Center, University of Iowa researchers involved in the study were senior author Dr. Ryan L. Boudreau, Assistant Professor of Internal Medicine – Cardiovascular Medicine; lead author Dr. Ryan M. Spengler, Postdoctoral Fellow; Dr. Xiaoming Zhang, Postdoctoral Fellow; Dr. Jared M McLendon, Postdoctoral Fellow; Dr. Jessica M Skeie, Research Scientist; Dr. Frances L. Johnson, Adjunct Associate Professor of Cardiology. Dr. Congsheng Cheng, Postdoctoral Fellow and Dr. Beverly L. Davidson, Arthur V. Meigs Chair in Pediatrics – The Children’s Hospital of Philadelphia, Professor of Pathology and Laboratory Medicine at The Raymond G. Perelman Center for Cellular and Molecular Therapeutics, Department of Pathology and Laboratory Medicine, the University of Pennsylvania
Sources Of Funding
American Heart Association [14SDG18590008 to R.L.B.]; Roy J. Carver Trust [University of Iowa to B.L.D.]; McLaughlin Trust [University of Iowa to F.L.J.]; National Institutes of Health [R01 NS076631 to B.L.D., T32 HL007638 to R.M.S., T32 HL007121 to J.M.M]. Funding for open access charge: Start-up funds.
Elucidation of transcriptome-wide microRNA binding sites in human cardiac tissues by Ago2 HITS-CLIP. Ryan M. Spengler, Xiaoming Zhang, Congsheng Cheng, Jared M. McLendon, Jessica M. Skeie, Frances L. Johnson, Beverly L. Davidson and Ryan L. Boudreau. Nucleic Acids Research. 2016, Vol.44, No. 15 doi 10.1093|narlgkw640
Published online July 14, 2016.
Read the full article at Nucleic Acids Research