For decades, researchers have focused most of their attention on protein-coding genes and proteins. With the completion of the human and mouse genomes and the accumulation of data on the mammalian transcriptome, the focus now shifts to non-coding DNA sequences, RNA-coding genes | Opinion The mammalian transcriptome and the function of non-coding DNA sequences Svetlana A Shabalina and Nikolay A Spiridonov Addresses National Center for Biotechnology Information National Library of Medicine National Institutes of Health Bethesda MD 20894 USA. Division of Therapeutic Proteins Center for Drug Evaluation and Research US Food and Drug Administration Bethesda MD 20892 USA. Correspondence Svetlana Shabalina. E-mail shabalin@ Published 25 March 2004 Genome Biology 2004 5 105 The electronic version of this article is the complete one and can be found online at http 2004 5M 105 2004 BioMed Central Ltd Abstract For decades researchers have focused most of their attention on protein-coding genes and proteins. With the completion of the human and mouse genomes and the accumulation of data on the mammalian transcriptome the focus now shifts to non-coding DNA sequences RNA-coding genes and their transcripts. Many non-coding transcribed sequences are proving to have important regulatory roles but the functions of the majority remain mysterious. Initial understanding of the profound differences between the mammalian proteome and the underlying transcriptome emerged in the 1970s with the discovery of RNA splicing and of the complex intron-exon structure of primary RNA transcripts. The importance of non-coding DNA was not readily accepted by the scientific community at the time of the discovery of the seemingly wasteful mechanisms of RNA processing whereby most of the primary transcript is edited out of the mature messenger RNA 1 . As the biological function of non-protein-coding DNA sequences was not understood the term junk DNA was coined and applied to most of the mammalian genome. The historic achievement of sequencing and annotating the complete human genome has revealed the complex landscape of mammalian non-coding DNA 2 . The subsequent sequencing of the complete genome of the mouse has not only provided a genetic .
