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Introns and Noncoding RNAs: The Hidden Layer of Eukaryotic Complexity

This chapter appears in the following book:

Noncoding RNAs: Molecular Biology and Molecular Medicine

Edited by: Jan Barciszewski and Volker A. Erdmann
ISBN: 0-306-47835-8
» Get more information about this book at landesbioscience.com «

Chapter authors:
John S. Mattick

Although it is not yet widely appreciated by the molecular biological community, the vast majority of the transcriptional output of the genomes of the higher organisms is noncoding RNA, composed of introns spliced out from protein-coding transcripts, and separate noncoding RNA transcripts that are developmentally regulated and which may also be spliced. Intronic RNAs comprise around 95% of the average protein-coding transcript in humans, and have high sequence complexity with interesting patterns of conservation, suggesting that these RNAs contain information that is expressed in parallel with protein-coding sequences. In addition there are thousands of noncoding RNA genes, which appear to account for at least half of all transcripts in humans, but most have not been studied, largely because there has been no expectation that such RNAs may be common or important, although evidence is rapidly emerging that they are both. Moreover, it is now evident that there are a number of complex genetic phenomena in the higher organisms, such as RNA interference, cosuppression, transgene silencing, methylation, imprinting, and transvection, which are related through intersecting pathways, and which are mediated by or connected to RNA signaling. It has also recently been shown that intronic and other noncoding RNAs are processed into multiple smaller species (snoRNAs and microRNAs), at least some of which are capable of carrying out trans-acting regulatory functions. It also appears that chromatin architecture is influenced by RNA signals. Taken together the available evidence suggests that, far from being evolutionary hangovers or curiosities, noncoding RNAs are central to the genetic control architecture of the higher organisms, and form a higher order system for gene regulation and gene-gene communication, which enables integration of complex networks of gene activity during eukaryotic differentiation and development, via RNA-DNA/chromatin, RNA-RNA and RNA-protein interactions. In addition, this system (the cis- and trans-acting RNA-based regulatory network) would be expected to have entirely different and generally much more subtle genetic signatures compared to protein coding sequences, and probably lies at the heart of quantitative trait variation and genetic susceptibility to disease, as opposed to the more severe phenotypes associated with loss of protein function.

John S. Mattick
ARC Special Research Centre for Functional and Applied Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia

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