l***d
发帖数: 1828 | 1 any comments?
http://www.nature.com/news/2011/110519/full/news.2011.304.html#
All science students learn the 'central dogma' of molecular biology: that
the sequence of bases encoded in DNA determines the sequence of amino acids
that makes up the corresponding proteins. But now researchers suggest that
human cells may complicate this tidy picture by making many proteins that do
not match their underlying DNA sequences.
In work published today in Science1, Vivian Cheung at the University of
Pennsylvania in Philadelphia and her team report that they have found more
than 10,000 places where the base (A, C, G or U) in a cell's RNA messages is
not the one expected from the DNA sequences used to make the RNA read-out.
When some of these 'mismatched' RNAs were subsequently translated into
proteins, the latter reflected the 'incorrect' RNA sequences rather than
that of the underlying DNA.
It was already known that some cells 'edit' RNA after it has been produced
to give a new coding sequence, but the new work suggests that such editing
occurs much more often in human cells than anyone had realized, and that
hitherto unknown editing mechanisms must be involved to produce some of the
changes observed. If the finding is confirmed by other investigators — and
some scientists already say they see the same phenomenon in their own data
— it could change biologists' understanding of the cell and alter the way
researchers study genetic contribution to disease.
Editing the central dogma
"The central dogma says that there is faithful transcription of DNA into RNA
. This challenges that idea on a much larger scale than was known," says
Chris Gunter, director of research affairs at the HudsonAlpha Institute for
Biotechnology in Huntsville, Alabama.
The work suggests that RNA editing is providing a previously unappreciated
source of human genetic diversity that could affect, for instance, how
vulnerable different people are to disease.
Cheung does not know whether there are heritable changes, passed down from
parent to child, that affect how much RNA editing occurs in different people
. But scientists already know of a handful of RNA editing proteins that play
a role in human health, such as the APOBEC enzymes, some of which have
antiviral activity. Researchers investigating the connection between
genetics and disease have been stymied by their inability to find strong
connections between genetic variation and risk for most common diseases,
leading researchers to wonder where the 'missing heritability' is hiding.
The new study at least provides one place to look.
"These events could explain some of the 'missing heritability' because they
are not present in everyone and therefore introduce a source of genetic
variation which was previously unaccounted for," says Gunter.
Living with error
But because they do not know what mechanism might be responsible, most
scientists contacted by Nature remained cautious about the significance of
the finding and its possible impact on biology. Some say it is possible that
technical errors could have caused the results. For instance, high-
throughput sequencing machines can make systematic errors in DNA and RNA
sequencing experiments.
And even if the findings hold up, it is still too early to know whether '
mismatching' plays an important role in human biology or not.
"The devil is in the details — to determine if the results are caused by
some unintended technical or computational flaw or are correctly describing
a biological phenomenon," says Thomas Gingeras at the Cold Spring Harbor
Laboratory in New York. "Assuming the latter, I would be encouraged to look
at our own large data sets to see if we see similar phenomenona."
Other researchers, such as Manolis Dermitzakis at the University of Geneva
in Switzerland, say they are seeing the phenomenon in their data. Indeed,
Cheung's team drew in part on data generated by the 1000 Genomes project, of
which Dermitzakis is a member. However, Dermitzakis says it is still
unclear how important the phenomenon is for disease susceptibility.
Cheung's group attempts to address many of these concerns, some of which
were raised when the preliminary work was presented last November (see 'DNA
sequence may be lost in translation') at the annual meeting of the American
Society for Human Genetics, in Washington DC. Since then, the team has been
looking for possible errors that could have caused the results.
For example, the researchers first observed DNA–RNA 'mismatches' in data
generated by next-generation sequencing technologies in the International
HapMap Project and the 1000 Genomes project. They have now confirmed some of
the putative DNA-to-RNA changes using traditional Sanger sequencing, and
have found the same changes in different people, across different cell types
, and reflected in proteins.
Cheung says that at first "we truly did not believe it". But after
performing the additional experiments "we cannot explain this by any obvious
technical errors, so we are pretty convinced that this is real," she says.
Researchers who study RNA editing, which up to now was known mostly from
plants and some unicellular human parasites, are intrigued by the new
finding.
Kazuko Nishikura of the Wistar institute in Philadelphia says she was
sceptical at first, because some of the base changes could not be explained
by previously identified mechanisms. But she was convinced once she saw
Cheung's data.
"It's really exciting, because this study reports a different variety of RNA
editing that is much more widespread than existing mechanisms," Nishikura
says.
References
1. Li, M. et al. Science doi:10.1126/science.1207018 (2011). | A******d
发帖数: 571 | | l***d
发帖数: 1828 | 3 和一个做human genetics聊过,觉得如果现象是真的,而且发现机理的话,会是一个很大
的突破,如果因为这个发现而在很多遗传病上有突破的话,可以拿奖了 | L**********O
发帖数: 1761 | | z*******a
发帖数: 175 | | A*****O
发帖数: 394 | 6 从这个研究可以看出，人类基因组计划及其后续计划是多么的重要！
没有这些数据，和谁比对？怎么比对？
那些守着自己那三亩田，到现在还嘀咕质疑着HGP重要性的伟大的小作坊生物学家们，
站高一点，看远一点，对自己的成长是有利的。
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【在 l***d 的大作中提到】
: any comments?
: http://www.nature.com/news/2011/110519/full/news.2011.304.html#
: All science students learn the 'central dogma' of molecular biology: that
: the sequence of bases encoded in DNA determines the sequence of amino acids
: that makes up the corresponding proteins. But now researchers suggest that
: human cells may complicate this tidy picture by making many proteins that do
: not match their underlying DNA sequences.
: In work published today in Science1, Vivian Cheung at the University of
: Pennsylvania in Philadelphia and her team report that they have found more
: than 10,000 places where the base (A, C, G or U) in a cell's RNA messages is
| l***d
发帖数: 1828 | 7 我觉得这个文章很有意思,说明DNA到RNA那一步不是100% faithful,那么对于一些遗传
变异的疾病的话,有可能并不是DNA mutated,而是RNA那一步mutated,如果发现相关机理
的话,对这一类疾病非常有指导意义,如果是真的,后续工作足以拿奖了. |
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