Sistem CRISPR baru untuk menargetkan RNA
Ditemukan pada bakteri sebagai mekanisme pertahanan virus, peneliti memprogram C2c2 untuk memanipulasi RNA seluler menggunakan CRISPR
Date:
June 2, 2016
Source:
Broad Institute of MIT and Harvard
Summary:
Para peneliti telah menandai sistem CRISPR baru yang menargetkan RNA , bukan DNA . Pendekatan baru memiliki potensi untuk membuka jalan yang kuat dalam manipulasi seluler .
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Para peneliti dari Broad Institute of MIT dan Harvard , Massachusetts Institute of Technology , National Institutes of Health , Rutgers University- New Brunswick dan Skolkovo Institut Sains dan Teknologi telah menandai sistem CRISPR baru yang menargetkan RNA , bukan DNA .
Pendekatan baru memiliki potensi untuk membuka jalan yang kuat dalam manipulasi seluler . Sedangkan DNA editing membuat perubahan permanen pada genom sel , pendekatan RNA - penargetan berbasis CRISPR dapat memungkinkan peneliti untuk melakukan perubahan sementara yang dapat disesuaikan atas atau bawah , dan dengan spesifisitas dan fungsi dari metode yang ada untuk interferensi RNA yang lebih besar
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New CRISPR system for targeting RNA
Discovered in bacteria as viral defense mechanism, researchers program
C2c2 to manipulate cellular RNA using CRISPR
Date:
June 2, 2016
Source:
Broad Institute of MIT and Harvard
Summary:
Researchers have
characterized a new CRISPR system that targets RNA, rather than DNA. The new
approach has the potential to open a powerful avenue in cellular manipulation.
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Researchers from the Broad Institute of MIT and Harvard, Massachusetts
Institute of Technology, the National Institutes of Health, Rutgers University-
New Brunswick and the Skolkovo Institute of Science and Technology have
characterized a new CRISPR system that targets RNA, rather than DNA.
The new approach has
the potential to open a powerful avenue in cellular manipulation. Whereas DNA
editing makes permanent changes to the genome of a cell, the CRISPR-based
RNA-targeting approach may allow researchers to make temporary changes that can
be adjusted up or down, and with greater specificity and functionality than
existing methods for RNA interference.
In a study published
today in Science, Feng Zhang and colleagues at the Broad Institute
and the McGovern Institute for Brain Research at MIT, along with co-authors
Eugene Koonin and his colleagues at the NIH, and Konstantin Severinov of
Rutgers University-New Brunswick and Skoltech, report the identification and
functional characterization of C2c2, an RNA-guided enzyme capable of targeting
and degrading RNA.
The findings reveal
that C2c2--the first naturally-occurring CRISPR system that targets only RNA to
have been identified, discovered by this collaborative group in October
2015--helps protect bacteria against viral infection. They demonstrate that
C2c2 can be programmed to cleave particular RNA sequences in bacterial cells,
which would make it an important addition to the molecular biology toolbox.
The RNA-focused action
of C2c2 complements the CRISPR-Cas9 system, which targets DNA, the genomic
blueprint for cellular identity and function. The ability to target only RNA,
which helps carry out the genomic instructions, offers the ability to
specifically manipulate RNA in a high-throughput manner--and manipulate gene
function more broadly. This has the potential to accelerate progress to
understand, treat and prevent disease.
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RNA , yang membantu melaksanakan instruksi genomik , menawarkan kemampuan untuk secara khusus memanipulasi RNA dengan cara a high-throughput manner--and manipulate gene function secara lebih luas . Ini memiliki potensi untuk mempercepat kemajuan untuk memahami , mengobati dan mencegah penyakit .
"C2c2 opens the
door to an entirely new frontier of powerful CRISPR tools," said Feng
Zhang, senior author, and Core Institute Member of the Broad Institute.
"There are an immense number of possibilities for C2c2 and we are excited
to develop it into a platform for life science research and medicine."
"The study of
C2c2 uncovers a fundamentally novel biological mechanism that bacteria seem to
use in their defense against viruses," said Eugene Koonin, senior author,
and leader of the Evolutionary Genomics Group at the NIH. "Applications of
this strategy could be quite striking."
Currently, the most
common technique for performing gene knockdown is small interfering RNA
(siRNA). According to the researchers, C2c2 RNA-editing methods suggest greater
specificity and hold the potential for a wider range of applications, such as:
- Adding
modules to specific RNA sequences to alter their function--how they are
translated into proteins--which would make them valuable tools for
large-scale screens and constructing synthetic regulatory networks, and
- Harnessing
C2c2 to fluorescently tag RNAs as a means to study their trafficking and
subcellular localization.
In this work, the team
was able to precisely target and remove specific RNA sequences using C2c2 --
lowering the expression level of the corresponding protein. This suggests C2c2
could represent an alternate approach to siRNA, complementing the specificity
and simplicity of CRISPR-based DNA editing and offering researchers adjustable
gene "knockdown" capability using RNA.
C2c2 has advantages
that make it suitable for tool development:
- C2c2 is
a two-component system, requiring only a single guide RNA to function, and
- C2c2 is
genetically encodable--meaning the necessary components can be synthesized
as DNA for delivery into tissue and cells.
"C2c2's greatest
impact may be made on our understanding the role of RNA in disease and cellular
function," said co-first author Omar Abudayyeh, a graduate student in the
Zhang Lab.
Story Source:
The above post is
reprinted from materials provided by Broad
Institute of MIT and Harvard. Note: Materials may be edited for content and length.
Journal Reference:
1.
Abudayyeh, O. et al. C2c2 is a single-component programmable
RNA-guided RNA-targeting CRISPR effector. Science, 2016
DOI: 10.1126/science.aaf5573