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Open Access Highly Accessed Research article

Intronic RNAs constitute the major fraction of the non-coding RNA in mammalian cells

Georges St Laurent12*, Dmitry Shtokalo23, Michael R Tackett2, Zhaoqing Yang2, Tatyana Eremina2, Claes Wahlestedt4, Silvio Urcuqui-Inchima1, Bernd Seilheimer5, Timothy A McCaffrey6 and Philipp Kapranov2*

Author Affiliations

1 Immunovirology – Biogenisis Group, University of Antioquia, Medellin, A.A. 1226, Colombia

2 St. Laurent Institute, One Kendall Square, Cambridge, MA, USA

3 A.P.Ershov Institute of Informatics Systems SB RAS, 6, Acad. Lavrentjev pr, Novosibirsk, 630090, Russia

4 University of Miami Miller School of Medicine, 1501 NW 10th Ave, Miami, FL, 33136, USA

5 Biologische Heilmittel Heel GmbH, Dr.-Reckeweg-Str. 2-4, Baden-Baden, 76532, Germany

6 Department of Medicine, Division of Genomic Medicine, The George Washington University Medical Center, 2300 I St. NW, Washington, DC, USA

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BMC Genomics 2012, 13:504  doi:10.1186/1471-2164-13-504

Published: 24 September 2012

Abstract

Background

The function of RNA from the non-coding (the so called “dark matter”) regions of the genome has been a subject of considerable recent debate. Perhaps the most controversy is regarding the function of RNAs found in introns of annotated transcripts, where most of the reads that map outside of exons are usually found. However, it has been reported that the levels of RNA in introns are minor relative to those of the corresponding exons, and that changes in the levels of intronic RNAs correlate tightly with that of adjacent exons. This would suggest that RNAs produced from the vast expanse of intronic space are just pieces of pre-mRNAs or excised introns en route to degradation.

Results

We present data that challenges the notion that intronic RNAs are mere by-standers in the cell. By performing a highly quantitative RNAseq analysis of transcriptome changes during an inflammation time course, we show that intronic RNAs have a number of features that would be expected from functional, standalone RNA species. We show that there are thousands of introns in the mouse genome that generate RNAs whose overall abundance, which changes throughout the inflammation timecourse, and other properties suggest that they function in yet unknown ways.

Conclusions

So far, the focus of non-coding RNA discovery has shied away from intronic regions as those were believed to simply encode parts of pre-mRNAs. Results presented here suggest a very different situation – the sequences encoded in the introns appear to harbor a yet unexplored reservoir of novel, functional RNAs. As such, they should not be ignored in surveys of functional transcripts or other genomic studies.