By continuing to explore the function and diversity of small RNAs, researchers may eventually tease apart their role in animal life over time and across lineages. “[O]ur results indicate that miRNAs and piRNAs, as classes of small riboregulators, have been present since the dawn of animal life, and indeed might have helped to usher in the era of multicellular animal life,” the authors wrote.
Rosetta Genomics, Johns Hopkins School of Medicine, Intradigm, Nature
Rosetta, Johns Hopkins Evaluate Lung miRNA Cancer Diagnostic
Rosetta Genomics said this week that it has begun a clinical assessment study of its microRNA-based miRview Squamous diagnostic, which is designed to differentiate squamous from non-squamous non-small cell lung cancer, with Johns Hopkins University School of Medicine.
"Having this microRNA-based test assessed for clinical validity by faculty at one of the country's top cancer research centers is viewed by us as a strong indication to the interest this product and our technology are generating in the oncology world,” Dalia Cohen, Rosetta’s CSO, said in a statement.
Rosetta anticipates launching miRview Squamous in the US this year.
Intradigm Raises $18.5M in Series B
Intradigm said this week that it has closed an $18.5 million Series B round of financing.
According to the company, the round was led by new investor Lilly Ventures, with participation by Roche Venture Fund and MP Healthcare Venture Management.
Intradigm said it will use the funds to advance its RNAi therapeutics platform. The company’s most developed drug candidate is the cancer therapy ICS-283, for which an investigational new drug application is slated to be filed this year (see RNAi News, 10/18/2007).
Researchers Trace Small RNAs Back to Early Animal Evolution
MicroRNAs and Piwi-interacting RNAs were present in the earliest animal lineages, new research suggests.
In a paper appearing in the advanced online publication of Nature this week, an international team of researchers looked for miRNAs and piRNAs in three groups of animals that diverged from the animal family tree before the development of bilateral symmetry. They detected both types of small RNAs in a sponge — which belongs to the earliest diverging group of animals — and in a starlet sea anemone — which belongs to a group diverging slightly later. Together, the results suggest that small RNAs were around early in animal evolution.
“It appears that both microRNAs and piRNAs have been available to shape gene expression throughout the evolution of animals and perhaps even helped to usher in the era of multicellular life,” senior author David Bartel, a biologist at the Whitehead Institute for Biomedical Research and Howard Hughes Medical Institute investigator, said in a statement.
While a lot is known about the presence or absence of miRNAs and piRNAs in animals with bilateral symmetry, it was unclear whether these small RNAs are found in more basal animal lineages, lead author and Bartel lab post-doc Andrew Grimson told RNAi News sister publication GenomeWeb Daily News.
In an effort to explore this, the researchers isolated 18- to 30-nucleotide RNAs from the starlet sea anemone Nematostella vectensis, a cnidarian, and sequenced complementary DNA libraries using high-throughput sequencing. They then flushed out miRNAs by looking for sequences that matched predictions based on bilateral miRNA pairing characteristics. “MicroRNAs make a very characteristic pattern,” Grimson said. “They really stand out.”
The researchers found 40 loci that matched all of the criteria for miRNA detection. Consistent with the notion that these represented miRNA, 31 of the loci mapped between known protein-coding genes and eight mapped within introns.
Even so, just one miRNA — miR-100 — seemed to be homologous to a bilaterian miRNA. And that miRNA contained a sequence shift that likely targets it differently in the starlet sea anemone than in other animals.
While previous research suggested that the sea anemone genome contained at least one miRNA, it was completely unknown whether the sponge — a “very, very early diverging organism” — contained any miRNAs, Grimson said.
To look even further back in evolutionary history, the researchers used the same approach to look for small RNAs in the demosponge, Amphimedon queenslandica. The researchers found eight miRNA in A. queenslandica — six mapping between protein-coding regions and two mapping within introns.
But there were differences between the miRNAs found in Nematostella and Amphimedon. For instance, the pre-miRNA hairpins found in the sponge were larger than those found in other animals. Meanwhile, those in the sea anemone were significantly smaller than bilaterian pre-miRNAs.
“In a relatively narrow spectrum of evolution microRNAs are often conserved,” Grimson said in a statement. “But in a broader spectrum they have completely changed. This suggests that microRNA evolution is more flexible and may be evolving more rapidly than suspected.”
Both Nematostella and Amphimedon also contained two classes of piRNAs. And although the researchers didn’t directly gauge miRNA or piRNA function in these animals, Grimson said, their genomes contain hallmarks suggesting that their piRNAs do target transposons.
Even so, miRNAs and piRNAs aren’t found in all animals. The researchers failed to detect either type of small RNA in Trichoplax adhaerans, a member of the placozoan group, which diverged after sponges. They did find proteins involved in the RNAi pathway, though, suggesting that miRNA genes may have been lost from the Trichoplax genome.
Whether or not miRNA contributes to bilateral complexity is still an open question, Grimson said. But, he added, the work illustrates that miRNAs and piRNAs are not a defining feature of bilaterians. Instead, the findings suggest that these small RNAs were available much earlier in animal evolution.