Biomol- artigo

FEBS Letters 585 (2011) 1600–1616

journal homepage: www.FEBSLetters.org

Review

The central role of RNA in human development and cognition
John S. Mattick
Institute for Molecular Bioscience, University of Queensland, Brisbane 4072, Australia

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a b s t r a c t
It appears that the genetic programming of humans and other complex organisms has been misunderstood for the past 50 years, due to the assumption that most genetic information is transacted by proteins. However, the human genome contains only about 20,000 protein-coding genes, similar in number and with largely orthologous functions as those in nematodes that have only 1000 somatic cells. By contrast, the extent of non-protein-coding DNA increases with increasing complexity, reaching 98.8% in humans. The majority of these sequences are dynamically transcribed, mainly into non-protein-coding RNAs, with tens if not hundreds of thousands that show specific expression patterns and subcellular locations, as well as many classes of small regulatory RNAs. The emerging evidence indicates that these RNAs control the epigenetic states that underpin development, and that many are dysregulated in cancer and other complex diseases. Moreover it appears that animals, particularly primates, have evolved plasticity in these RNA regulatory systems, especially in the brain. Thus, it appears that what was dismissed as ‘junk’ because it was not understood holds the key to understanding human evolution, development, and cognition. Ó 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Article history: Received 29 April 2011 Accepted 3 May 2011 Available online 6 May 2011 Edited by Sergio Papa, Gianfranco Gilardi and Wilhelm Just Keywords: Non-coding RNA Evolution Gene regulation Epigenesis RNA editing Retrotransposition

1. Introduction The purpose of this article is to make the case that the genomic programming of humans and other complex