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The mammalian genome as an RNA machine
Author(s) -
Mattick John S,
Croft Larry J,
Pheasant Michael,
Mercer Tim R,
Dinger Marcel E
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.397.3
Subject(s) - rna , biology , genome , multicellular organism , chromatin , rna splicing , genetics , computational biology , epigenetics , transcription (linguistics) , non coding rna , gene , linguistics , philosophy
It appears that the genetic programming of the higher organisms has been fundamentally misunderstood for the past 50 years. It is now evident that the majority of the mammalian genome is transcribed, apparently in a developmentally regulated manner, and that most complex genetic phenomena in the higher organisms are RNA‐directed. Evidence will be presented (i) that regulation scales quadratically with function in integrated systems, including organisms, and that multicellular eukaryotes have solved this problem by the cooption of RNA as an analog‐digital regulatory system; (ii) that much, if not most, of the mammalian genome is not evolving neutrally, but is comprised of different types of sequences evolving at different rates under different structure‐function constraints; and (iii) that there are thousands of non‐protein‐coding transcripts in mammals that are dynamically expressed during differentiation, many of which show precise expression patterns and subcellular localization in different regions of the brain. These and other observations suggest that the majority of the mammalian genome is devoted to a hidden RNA regulatory system that directs developmental trajectories by controlling chromatin architecture and epigenetic memory, transcription, splicing, RNA modification and editing, mRNA translation and RNA stability. ( This work was supported by the Australian Research Council ).