The transcriptional output for the vast majority of complex genomes, including the human genome, includes non-protein-coding RNA (Mattick 2001). These noncoding RNAs appear to be involved in a variety of cellular roles, ranging from simple housekeeping to complex regulatory functions. Long noncoding RNA and microRNA (miRNA) have become a focus of current research.
Of the various subclasses of noncoding RNAs, microRNAs (miRNAs) are the most thoroughly characterized. miRNAs are single-stranded, 19 to 25 nucleotide RNAs and are thought to regulate gene expression posttranscriptionally by binding to the 3’ untranslated regions (UTRs) of target mRNAs, inhibiting their translation (Ambros 2004). Recent experimental evidence suggests that the number of unique miRNAs in humans could exceed 800 (Bentwich 2003), though several groups have hypothesized that there may be up to 20,000 (Okazaki 2002) noncoding RNAs that contribute to eukaryotic complexity.
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miRNA Expression Profiling Experimental Planning and Design
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Long ncRNA (>200 nt)
Recent data suggest that there are thousands of long noncoding RNAs (ncRNAs) that are expressed in a developmentally regulated manner in mammals, whose functions have yet to be studied but which appear to play important roles in gene regulation, especially epigenetic regulation. Both cDNA and tiling array studies have indicated that the majority of the mammalian genome is transcribed, often from both strands, to produce overlapping and interlacing transcripts, many of which are cell- and tissue specific.
A large fraction of these transcripts are dynamically expressed in differentiating cells, including embryonal stem cells, neural stem cells, muscle cells, macrophages, and T cells, as well as in the brain, and show specific subcellular locations. While most have yet to be studied, there is increasing evidence that these transcripts are important in development and brain function, and that their expression is perturbed in diseases such as cancer. These transcripts appear to represent a vast hidden layer of genetic programming in mammals, and a new frontier of molecular genetic, molecular biological, physiological, and cell biological research.
Noncoding RNA References
Amaral, P.P. et al. The eukaryotic genome as an RNA machine. Science 2008; 319: 1787-1789.
Amaral, P.P. and Mattick, J.S. Noncoding RNA in development. Mamm Genome 2008; in press.
Carninci, P. et al. The transcriptional landscape of the mammalian genome. Science 2005; 309: 1559-1563.
Dinger, M.E. et al. RNAs as extracellular signaling molecules. Journal of Molecular Endocrinology 2008; 40: 151-159.
Dinger, M.E. et al. Long noncoding RNAs in mouse embryonic stem cell pluripotency and differentiation. Genome Research 2008; 18: 1433-1445.
Dinger, M.E. et al. NRED: a database of long noncoding RNA expression. Nucleic Acids Research 2009; in press.
Mattick, J.S. and Makunin, I.V. Non-coding RNA. Human Molecular Genetics 2006; 15: R17-29.
Mehler, M.F. and Mattick, J.S. (2007) Noncoding RNAs and RNA editing in brain development, functional diversification, and neurological disease. Physiology Review 2007; 87: 799-823.
Mercer, T.R. et al. Specific expression of long noncoding RNAs in the mouse brain. Proceedings of the National Academy of Sciences 2008; 105: 716-721.
Rinn, J.L. et al. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 2007; 129: 1311-1323.
Yu, W. et al. Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA. Nature 2008; 451: 202-206.
Ambros, V. The Functions of Animal microRNAs. Nature. 2004 ; 431: 350–355.
Bentwich, I. et al. Identification of Hundreds of Conserved and Nonconserved Human microRNAs. Nature Genetics. 2005; 37: 766–770.
Mattick, J.S. Non-coding RNAs: the Architects of Eukaryotic Complexity. European Molecular Biology Organization Reports. 2001; 2(11): 986–991.
Okazaki, Y. et al. Analysis of the Mouse Transcriptome Based on Functional Annotation of 60,770 Full-length cDNAs. Nature. 2002 ; 420.