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Nature Study Vindicates ENCODE, Reports Functions for Antisense Non-Coding “Junk” RNA

Last month we reported on the results of the ENCODE project which found that over 80% of the genome is transcribed, making it associated with a biochemical function. While the results of the ENCODE project continue to be rejected by a small cadre of vocal evolution-defenders who live mostly on the Internet, scientific researchers continue to discover more and more functions for all the non-coding RNA that is being transcribed. A recent paper in Nature observes that ENCODE’s results are leading scientists to understand what non-coding DNA is doing:

Most of the mammalian genome is transcribed. This generates a vast repertoire of transcripts that includes protein-coding messenger RNAs, long non-coding RNAs (lncRNAs) and repetitive sequences, such as SINEs (short interspersed nuclear elements). A large percentage of ncRNAs are nuclear-enriched with unknown function. Antisense lncRNAs may form sense-antisense pairs by pairing with a protein-coding gene on the opposite strand to regulate epigenetic silencing, transcription and mRNA stability.

(Carrieri et al., “Long non-coding antisense RNA controls Uchl1 translation through an embedded SINEB2 repeat,” Nature (2012), doi:10.1038/nature11508 )

The paper finds that antisense DNA from Uchl1, a gene involved in brain function in mice (and probably other mammals), helps to regulate and increase “protein synthesis at a post-transcriptional level, hereby identifying a new functional class of lncRNAs.” An article at Science Daily about the paper reports as follows:

To synthesize proteins, the DNA needs RNA molecules serving as short “transcriptions” of the genetic information. The set of all these RNA molecules is called “transcriptome.” In the human transcriptome, along with around 25 thousand sequences of coding RNA (i.e. the sequences involved in the synthesis process), an even larger number of non-coding RNA sequences can be found. Some of these RNAs are called “antisense” because they are complementary to sequences of coding RNA called “sense” (the pairing of a sense and an antisense RNA can be seen as a zip).

[Researchers] previously discovered that many of the protein coding genes have corresponding antisense RNAs. A study published in Nature, coordinated by a group of SISSA researchers in Trieste, Italy, has now found that a particular type of antisense RNAs stimulate the translation of the protein coding mRNAs that they overlap to. This is in sharp contrast with the current belief that antisense RNAs are universally associated to negative regulation of protein translation.

Science Daily quotes one of the scientists who co-authored the paper, stating that this finding overturns the notion of “junk” RNA in the genome:

We are delighted to see that there is one more function for long non-coding RNAs,” says Piero Carninci, Team Leader at RIKEN OSC. “Since the initial discovery that the majority of the genome produces so many non-coding RNAs, there has been a general skepticism related to the possible function of these RNAs. This is a milestone study identifying a novel class of non-coding RNAs which have a key regulatory function, enhancing protein translation. Additionally, this function is mediated by repetitive elements, so far generally considered the ‘junk’ fraction of the genome, suggesting that the concept that most of the genome is ‘junk’ should be revisited. After all, there may be function embedded in any part of the genome, which we do not yet understand.”

The Nature paper concludes: “These data reveal another layer of gene expression control at the post-transcriptional level.” They also reveal yet another reason to take the results of ENCODE seriously.