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Yet More "Junk DNA" Not-so-Junk After All

Proponents of intelligent design (ID) have long predicted that many of the features of living systems which are said to exhibit "sub-optimal" design will, in time, turn out to have a rationally engineered purpose. This is one of several areas where ID actively encourages a fruitful research agenda, in a manner in which neo-Darwinian evolution does not. One such area, and a field for which I have long held an inquisitive fascination for, is the subject of so-called "junk DNA," and the non-coding stetches of RNA which are transcribed from them.

Skepticism of the "junk DNA" paradigm is not a phenomenon which is limited to proponents of ID. This popular view of the genome -- while still resonating as the conventional view among neo-Darwinian thinkers -- has also been challenged by John Mattick of the University of Queensland and Jim Shapiro of the University of Chicago.

Earlier this month, an article appeared in the journal Cell by a Spanish team. The article announced the discovery of the ability of long non-coding RNA, which are often encoded in DNA near genes known to be important to both stem cells and cancer, to serve as enhancer elements (which promote gene expression).

According to the paper's Abstract:

While the long noncoding RNAs (ncRNAs) constitute a large portion of the mammalian transcriptome, their biological functions has remained elusive. A few long ncRNAs that have been studied in any detail silence gene expression in processes such as X-inactivation and imprinting. We used a GENCODE annotation of the human genome to characterize over a thousand long ncRNAs that are expressed in multiple cell lines. Unexpectedly, we found an enhancer-like function for a set of these long ncRNAs in human cell lines. Depletion of a number of ncRNAs led to decreased expression of their neighboring protein-coding genes, including the master regulator of hematopoiesis, SCL (also called TAL1), Snai1 and Snai2. Using heterologous transcription assays we demonstrated a requirement for the ncRNAs in activation of gene expression. These results reveal an unanticipated role for a class of long ncRNAs in activation of critical regulators of development and differentiation.

The researchers mapped the noncoding RNA loci within the genome, observing that the noncoding RNAs are preponderantly located in close proximity to genes which are responsible for influencing how stem cells specifically differentiate into multiple cell types. To the surprise of the researchers, it was observed that depriving a cell of these long non-coding RNAs results in a decrease in the overall gene expression of the nearby genes. When the adult stem cells were depleted of a particular long ncRNA (called nc-RNA-activating 7), it had the same effect as depleting the protein product of a nearby gene (Sna1) which regulates how cells migrate. This was argued to be indicative of the role of long noncoding RNAs in potentiating gene expression, in contrast to so-called microRNAs, which are well known for their involvement in gene silencing. The physorg report notes that, "Their studies further showed that inserting an ncRNA next to a gene for luciferase--the enzyme responsible for a firefly's glow--increased the amount of protein produced by that gene in cells grown in culture. While not all long ncRNAs may act like enhancers, the majority of the ones the team studied do, Shiekhattar says."

The paper concludes with a prediction regarding a proposed mechanism for the enhancer-like functions which have been associated with these sequences

We envision a mechanism by which ncRNAs by virtue of sequence or structural homology targets the neighboring protein-coding genes to bring about increased expression. Our experimental evidence using a heterologous promoter point to the mechanism of action for activating ncRNAs operating in cis. However, genome-wide analysis following depletion of ncRNA-a7 suggested changes in gene expression that may not be related to the action of ncRNA-a7 on its local environment and may be a result of wider trans-mediated effects of ncRNA-a7. Such regulatory functions of ncRNAs could be achieved through an RNA-mediated recruitment of a transcriptional activator, displacement of a transcriptional repressor, recruitment of a basal transcription factor or a chromatin-remodeling factor. While we favor a transcriptional based mechanism for ncRNA activation, effects on RNA stability cannot be excluded. Taken together, the next few years will bring about new prospects for the long ncRNAs as central players in gene expression. [emphasis mine]