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

Abstract

BackgroundThe 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.ResultsWe 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.ConclusionsSo 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.

Maternal Plasma RNA Sequencing for Genome-Wide Transcriptomic Profiling and Identification of Pregnancy-Associated Transcripts

“…Second, we have focused only on the reference transcripts and have not yet explored individual isoforms. Future studies could include detection of novel transcripts and differential analysis of the splicing variants and their isoforms (32)(33)(34) by increasing the sequencing read depth. Third, we have omitted ASE filtering in the analysis of proportions of fetal-and maternal-derived transcripts for the early pregnancy samples, because the chorionic villi and amniotic fluid had been exhausted for the genotyping analysis.…”

Comparative Analysis of Intronic Noncoding RNA Genes among Organisms

“…These mechanisms for expression regulation of ncRNA genes suggest that some expression regulation of ncRNA genes depend on gene locations in genomic DNA sequences. Such researches for intronic ncRNA genes have shown that many ncRNA genes are located in intronic regions [18][19][20][21]. Therefore, we should classify ncRNA genes based on gene locations in genomic sequences.…”

A Comprehensive Review of Emerging Computational Methods for Gene Identification

“…With more and more genes being identified and annotated, some gene-related issues [6] are being studied, some of which are as follows: the identification of alternative splicing sites that determine the loci of introns and exons [155,156]; novel protein-coding prediction, which aims to find novel protein coding regions [136]; ncRNA prediction, which focuses on long or small regulatory ncRNA [157][158][159] in so-called intergenic regions; and finding other functionally non-genic elements that mainly exist in non-genic areas and play an active role in regulating gene expression [160]. Furthermore, some important biological signals are considered to be relevant to gene structures, such as polymorphism, CpG island, and Methylation, etc.…”