Robert Karl Stonjek
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 Posted: Tue Jul 22, 2008 6:33 pm Post subject: News: RNA in control |
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RNA in control
Posted by Megan Scudellari
[Entry posted at 17th July 2008 07:55 PM GMT]
An ancient RNA molecule is the answer to a bacterial mystery,
according to a study published in Science tomorrow (July 18). Researchers
have identified the binding molecule of a key messenger in bacteria, but to
their surprise, the molecule was not a protein -- traditionally thought of
as regulators of cellular processes -- but a unique RNA trigger.
In the last six years, RNA triggers, called riboswitches, have emerged
as surprising regulators of gene expression -- a role previously ascribed
almost exclusively to proteins. "I think if in 2001 you were proposing that
bacteria were loaded with flavors of riboswitches" that manipulate genetic
expression, said Ron Breaker of Yale University and senior author of the
paper, "you>d lose all scientific credibility."
The riboswitch his group identified, which binds the bacterial second
messenger cyclic di-GMP, is the newest addition to a string of recent
riboswitch discoveries. But it is especially interesting, said Sebastian
Doniach, a biophysicist at Stanford studying the structure of riboswitches,
because "cyclic di-GMP is a more general substrate than those of previous
riboswitches." It regulates many different pathways in a variety of cells,
something not seen in other classes of riboswitches, said Doniach, who was
not involved in the study.
Cyclic di-GMP, a circular molecule made of two RNA nucleotides, is
ubiquitous in bacteria and involved in a range of various functions
including motility, morphology, and virulence. But how it regulates gene
expression was not known until Breaker>s lab stumbled upon the answer.
Breaker, a Howard Hughes Medical Institute investigator, and colleague
Zasha Weinberg designed a computational pipeline of computer algorithms to
sift through bacterial genomes for the signature of riboswitches, bits of
RNA that function by binding single, specific ligands to alter gene
expression. Last year, their technique produced a riboswitch candidate
called the GEMM motif (Genes for the Environment, for Membranes and for
Motility), but they were having trouble identifying the associated ligand.
GEMM is implicated in multiple pathways, as its name suggests, and the two
biologists knew of no single ligand that was involved in them all.
One day in a game of "guess the ligand," Breaker and Weinberg began
listing the multiple pathways to each other while arguing that no connection
amongst them made sense. That>s when research scientist Narasimhan Sudarsan
strode into the room, Breaker recalled. Sudarsan held up a finger, quieting
the two men, and said, "I know what the ligand is." Sudarsan, who was
familiar with cyclic di-GMP, knew the small molecule had been detected in
many of the same pathways as GEMM. Three days later, he came back with proof
that the ligand was cyclic di-GMP, said Breaker. "He knew a lot of the
literature," said Breaker, "and he drew the connection."
The team performed both biochemical and genetic analyses of GEMM
regions in Vibrio cholerae, Bacillus cereus and Clostridium difficile to
determine that cyclic di-GMP was indeed the ligand for the riboswitch. In V.
cholerae, the two RNA molecules tag-team to control expression of a protein
critical for the bacteria>s ability to infect mammals. That new information
raises the possibility that these RNA mechanisms may hold clinical
potential, but "we>re a long way from the leap to make analogs to trick the
riboswitch," said Breaker.
His team hypothesizes that riboswitches are ancient genetic regulators
that emerged early on; although proteins eventually took over the show,
today the RNA molecules remain highly conserved. At this point, more than 20
classes of metabolite-sensing riboswitches have been discovered in all three
domains of life, and the search for more continues. "I think there>s a lot
more out there nobody has found yet," said Doniach.
Source: TheScientist
http://www.the-scientist.com/blog/display/54835/
Posted by
Robert Karl Stonjek |
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