SUN-030 Expression Profiles of Short RNAs in Mouse Serum Employing Endocrine Organs as Controls

Over 90% of the human genome expresses many different forms of non-protein-coding (nc) RNAs in addition to mRNAs. They are categorized into short and long ncRNAs. Although their overall functions and biological importance are still under investigation, they appear to be essential for supporting complex human activities mainly by regulating genome transcription and/or protein translation. It is known that some short RNAs are identified in several body fluids of humans, including serum, urine and saliva. Biological and/or pathological roles of serum micro (mi) RNAs have recently been reported, whereas little is known about other short non-coding (snc) RNAs circulating in serum. Here we present a comprehensive analysis on the short RNAs present in mouse serum using the RNA-sequencing by employing two endocrine organs (adrenal gland and ovary) and liver as controls. We found that serum has numerous short RNA reads and most of them (~90%) are unable to be mapped to the reference genome. Among the mapped reads, short RNAs expressed from the intergenic area (intergenic sncRNAs) represent the majority (97.7%) of short RNAs appeared in mouse serum. These intergenic sncRNAs are mapped to the intergenic area located closely to the nearby protein-coding genes (~20 kb distance), indicating their potential regulatory functions on the transcription of these coding genes. Most of the serum intergenic sncRNAs are distinct from those identified in the three control organs, whereas the intergenic sncRNAs found in the control organs highly overlap with each other. Among known sncRNAs, fragments of ribosomal (r) RNAs (72.0%), transfer (t) RNAs (18.1%), piwi-interacting (pi) RNAs (4.01%) and micro (mi) RNAs (3.96%) are most abundant, whereas small nuclear (sn) RNAs (1.46%) and small nucleolar (sno) RNAs (0.44%) are found as minor fractions. Very few short RNAs derived from mRNAs or long non-coding RNAs are also identified in mouse serum. Interestingly, many of the mRNA fragments identified in serum are derived from the genes associated with the transmembrane signaling pathways in the Ingenuity(®) Pathway Analysis, suggesting easy liberation of these mRNA fragments from respective cells possibly due to their local translation as reported in neuronal cells. Taken together, our findings indicate that sncRNAs, particularly intergenic sncRNAs, rRNA fragments and tRNAs, are abundant in mouse serum. These results suggest in humans that they may have important biological actions and/or potential clinical implications as valuable clinical markers/therapeutic targets in addition to miRNAs.