Newfound world of tiny RNA proves huge
Molecular biologists are going to have to rethink transcription, said a
leading RNA expert today. Tiny RNA - RNA that is only about 22 nucleotides
long - is big news.
Overnight, the number of known members of the tiny RNA family, known to play a
role in regulating gene expression, has ballooned from two to more than 70.
But it won't stop there says Volker Erdmann, professor at the Free University
in Berlin. "This is just the peak of an iceberg," Erdmann told BioMedNet News
Erdmann was responding to news that three separate research teams in the US
and Germany have simultaneously unearthed a huge family of evolutionarily
conserved tiny RNA molecules.
Erdmann, one of few RNA experts not involved in these projects, says that his
own research with tiny RNA suggests these molecules will be of "great value"
in the future of molecular medicine.
Two tiny RNA molecules called lin-4 and let-7, the full extent of the family
identified to date, had previously been shown to switch off mRNA translation
during different stages of Caenorhabditis elegans development. But a team led
by David Bartel at the Massachusetts Institute of Technology has unearthed a
massive 55 previously unknown tiny RNAs from C. elegans.
Another team, led by Victor Ambros at the Dartmouth Medical School in Hanover,
New Hampshire, independently identified 15 tiny RNAs (including many found by
Bartel). Ambros also found three sequences with apparent homologs in insects
A third team showed that humans also have tiny RNA. A team led by Tom Tuschl
at the Max Planck Institute for Biophysical Chemistry in Göttingen, Germany,
identified 19 different tiny RNAs in human cells, as well as 14 in Drosophila.
Tiny RNA molecules may have gone unnoticed both precisely because they are
tiny, suggests David Bartel, and also because they are RNA.
"Most people haven't been looking for 'riboregulators'," Bartel told BioMedNet
News. "If they're looking for something that is modulating gene expression,
they would expect it to be a protein." So biochemists would have overlooked
Molecular biologists, on the other hand, would have encountered the size
problem. "These very, very small RNAs would have run off the bottoms of gels
in most searches for expressed RNAs," said Bartel. So the tiny RNAs lay
Tuschl and Bartel were already aware of each others' work, but Ambros had to
write up his results quickly when he found out what was going on. The
manuscripts from all three teams were accepted for publication in Science, but
since they had all invented different names for their tiny RNAs, the journal
asked them to come up with a uniform nomenclature.
"We had a great time coordinating things," said Ambros. They settled on
Bartel's suggestion of ditching the tiny in favor of micro; the molecules are
now called microRNAs. ("Micro sounds more official," said Ambros.) The results
of all three teams appear tomorrow in Science.
Ambros says the accumulated data barely scratch the surface of the microRNA
world. He estimates there are at least 200 microRNAs in C. elegans alone, with
about 5-10% conserved in human and mouse genomes. He expects homologs will
also be found in plants, and is about to start looking for them in fungi.
Researchers will eagerly seek the function of these very small RNAs. Ambros
and Bartel expect that they will extend well beyond the post-transcriptional
function of lin-4 and let-7, the only microRNAs investigated so far.
One obvious question, given discovery of a whole new gene class, is whether
any members could be involved in human disease. People usually search for
disease genes among protein coding sequences, Ambros says. Once again, tiny
RNAs are being overlooked.
"Hopefully human geneticists are paying attention," said Ambros.
--- --- --- --- ---
Useless hypotheses, etc.:
consciousness, phlogiston, philosophy, vitalism, mind, free will, qualia,
analog computing, cultural relativism, GAC, Cyc, Eliza, cryonics, individual
uniqueness, ego, human values, scientific relinquishment, malevolent AI
We move into a better future in proportion as science displaces superstition.
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