Despite amazing progress in the analysis of the genome, the role of as much as 95 percent of human DNA is still unclear; the genes or coding regions represent only a very small proportion of the total sequence. Some of the rest specifies the production of long non-coding RNA (ncRNA). Now a new study recently published in Cell sheds new light on the distribution of nc-RNA molecules, and suggests a potential role in the regulation of gene expression.
The researchers mapped the ncRNA sites within the genome using GENCODE, a database that annotates the human genome with currently available scientific evidence. They found 3,000 ncRNA sites within the genome and estimated that there could be a total of 10 to 12,000 such sequences in human DNA. Interestingly, this is comparable with about 20,000 genes known to encode proteins [Ørom UA et al. (2010) Cell 143(1):46-58].
The ncRNA sites were mostly in close proximity to genes critical for cell development and differentiation, and the long ncRNAs themselves were found to be present in a variety of cell types. Depletion of a number of ncRNAs led to decreased expression of their neighbouring protein-coding genes, revealing a possible role for ncRNAs in regulating gene expression, acting as gene enhancer elements - short regions of DNA that can promote gene transcription. The concept of gene enhancers has been known for decades but there has been no consensus how they might work; improved understanding may reveal new therapeutic avenues for conditions such as cancer.
The results of this study add to the ever-growing body of evidence that the classic ‘central dogma’ of molecular biology is incomplete. This original dogma set out a unidirectional flow of information from DNA transcribed into RNA, then translated into proteins. In recent years, however, studies have shown that a significant portion of transcribed RNA molecules are not translated into proteins, but play various regulatory roles in the cell.