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“Junk” RNA Found to Encode Peptides That Regulate Fruit Fly Development

Jonathan McLatchie

Advocates of intelligent design have long been skeptical of the claim that the majority of our genome is nonfunctional gibberish, a mere relic of our evolutionary past. Many of the key arguments for common ancestry are based around the supposition that certain loci of our genome are functionless. But the gaps in our knowledge of the genome (in which such supposition resides) are continually shrinking.

A recent paper published in Science by Kondo et al. reported on the discovery that some of the supposed “non-coding” regions of the RNA transcript actually actively encode for short peptides that regulate genes involved in Drosophila development.

According to the Abstract,

A substantial proportion of eukaryotic transcripts are considered to be noncoding RNAs because they contain only short open reading frames (sORFs). Recent findings suggest, however, that some sORFs encode small bioactive peptides. Here, we show that peptides of 11 to 32 amino acids encoded by the polished rice (pri) sORF gene control epidermal differentiation in Drosophila by modifying the transcription factor Shavenbaby (Svb). Pri peptides trigger the amino-terminal truncation of the Svb protein, which converts Svb from a repressor to an activator. Our results demonstrate that during Drosophila embryogenesis, Pri sORF peptides provide a strict temporal control to the transcriptional program of epidermal morphogenesis.

The paper states that,

We and others recently identified an evolutionarily conserved sORF gene, referred to as polished rice ( pri) or tarsal-less (tal) in Drosophila, and mille-pattes (mlpt) in Tribolium (9-11). primRNA is a polycistronic transcript that encodes four similar peptides, 1 to 32 amino acids in length, that play a redundant role in Drosophila embryogenesis (9, 10). Embryos that lack pri display prominent defects, including the absence of trichomes and aberrant tracheal architecture (9, 10). Reduced pri activity in imaginal development results in abnormal leg morphogenesis (10, 12). Similarly, mlpt knockdown in Tribolium leads to appendage defects and the transformation of segmental identity (11).

The gene containing the Short Open Reading Frame (sORF) is a polycistronic transcript (meaning it carries the information of several genes, which are translated into multiple proteins) from a gene called polished rice, so named because the flies that have a mutation in the gene lack characteristic hairs in the fly embryo which resemble grains of rice. The researchers found that this RNA transcript encodes for four short peptides, ranging from 1 to 32 amino acids long.

The researchers report their finding “that the polished rice peptides trigger the truncation of a protein called Shavenbaby, which regulates the development of the hairs.”

A related report by Nature News makes the following comment:

Short peptides could be lurking virtually anywhere in the genome, says Desplan. Sequence analysis suggests that DNA regions capable of encoding tiny peptides exist in front of many protein-coding genes, but few researchers believe that these regions are doing anything useful, he adds.

The article further comments,

Meanwhile, Gerstein notes that the polished rice peptides could also have implications for how we view pseudogenes, which have long been thought to be defunct relics of protein-coding genes. Pseudogenes often contain many signals that would stop protein synthesis and, as a result, could only encode short amino-acid chains. “Maybe this would provide a new way for pseudogenes to have some sort of function,” he says.

The researchers conclude,

Besides the mechanisms of epidermal differentiation, our studies suggest broader functions for Pri peptides. Although pri is also required for tracheal morphogenesis (9), we observed normaltrachea in svb mutant embryos (fig. S9), indicating that Pri peptides probably regulate additional developmental factors. Recent large-scale analyses indicate that thousands of unexplored transcripts are also probably encoding polypeptides of less than 100 amino acids in mice and humans (1, 21, 7). Future functional analyses should elucidate how small peptides encoded by transcripts improperly termed ncRNAs contribute to various biological processes including development and differentiation. [Emphasis mine]