Poster abstracts

Poster number 26 submitted by Colton Martens

Small Noncoding RNAs in Heart Failure

Colton Martens (Physiology and Cell Biology; The Ohio State University), Jonathan Howard (The Center for Molecular Biology of RNA; University of California, Santa Cruz), Andrew Holmes (The Center for Molecular Biology of RNA; University of California, Santa Cruz), Todd Lowe (The Center for Molecular Biology of RNA; University of California, Santa Cruz), Federica Accornero (Physiology and Cell Biology; The Ohio State University)

Abstract:
A wide variety of functional small noncoding RNA (ncRNA) species have been uncovered in recent decades, and they have revolutionized our understanding of gene regulation and disease pathogenesis. High-throughput RNA sequencing has allowed researchers to rapidly evaluate the RNA composition of diseased tissues, which has played an integral role in our understanding of gene misregulation during disease. Unfortunately, many RNA species are densely packed with post-transcriptional modifications that block reverse transcription and make them difficult to sequence. Our laboratory has recently employed a technique called ARM-Seq (AlkB-facilitated RNA methylation sequencing) to determine if small RNA populations are altered in failing human hearts. ARM-Seq involves treatment of RNA with a demethylase enzyme (AlkB) that removes methyl modifications from nucleotides.1 This greatly enhanced the sequenceability of many RNA species, and we found that many classes of small ncRNA were highly altered during heart failure. These include small nucleolar RNAs, tRNA fragments, rRNA fragments, 7SK RNA, and 7SL RNA. Interestingly, many of these RNA species are implicated in translational regulation and cell growth, both of which are known to be misregulated during heart failure. Moreover, many of these RNA species are poorly studied in the context of heart failure and could thus represent an exciting new line of research in cardiac disease. We are currently working to validate the sequencing results and will then focus on characterizing the functions of RNA species of interest.

References:
Cozen, A. E. et al. ARM-seq: AlkB-facilitated RNA methylation sequencing reveals a complex landscape of modified tRNA fragments. Nature Methods 12, 879 (2015)

Keywords: noncoding RNA, small RNA