MON-718 Abundant Circulation of Functional Short Non-Coding RNAs Expressed from the Intergenic Area in Mouse Serum

Abstract

The human genome expresses numerous and different forms of non-protein-coding (nc) RNAs from over 80% of its sequence in addition to mRNAs. Although their overall functions and biological importance are still under intensive investigation, they appear to be important for supporting complex human biology. Some of these ncRNAs are recently identified in several human fluids, such as serum, urine and saliva. Here we present a comprehensive analysis on the short RNAs presented in mouse serum by employing three organs, adrenal gland, liver and ovary, as controls. We found that serum has numerous sRNAs. Among them, short ncRNAs (sncRNAs) expressed from the intergenic area (intergenic sncRNAs) dominated the majority (~97%) in serum with their read numbers equivalent to those found in three control organs. In contrast, known sncRNAs, such as ribosomal RNA fragments, transfer RNAs, micro RNAs, piwi-interacting RNAs, small nuclear and small nucleolar RNAs, were very minor components in serum, and were significantly low compared to control organs. Few short RNA fragments derived from mRNAs or long non-coding RNAs were also identified. The principal component analysis for the intergenic sncRNAs found in serum and three control organs revealed that the former was distinct from the latter. Indeed, ~90% of serum intergenic sncRNAs were not identified in each control organ in one-by-one comparisons. Multiple comparison between serum and all three control organs demonstrated a similar tendency: ~75% of the serum intergenic sncRNAs were distinct from the intergenic sncRNAs found in the three control organs, whereas these control organs shared 53% of them. The genomic areas encoding these intergenic sncRNAs tended to distribute around -20 - +20 kbs from the transcription start site of their nearby protein-coding genes. Among four selected serum intergenic sncRNAs, overexpression of the one located closely to the olfactory receptor 1322 gene exerted in a mouse hepatoma cell line the robust transcriptional regulatory activity on ~100 protein-coding genes that were accumulated in several distinct biological pathways. Our results indicate that mouse serum contains biologically active intergenic sncRNAs in addition to other known forms. The results also suggest their potential biological importance and/or usefulness in disease diagnosis and treatment in humans.