Programmable RNA N6-methyladenosine editing by CRISPR-Cas9 conjugates
| Autor: | Yuanhui Mao, Shu-Bing Qian, Jun Zhou, Xiao-Min Liu, Quanquan Ji |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Gene Editing
0303 health sciences Messenger RNA Methyltransferase Adenosine Base Sequence Cas9 030302 biochemistry & molecular biology RNA Cell Biology Methylation Computational biology Methyltransferases Article 3. Good health Cell Line 03 medical and health sciences CRISPR Humans Guide RNA RNA Messenger CRISPR-Cas Systems Molecular Biology Function (biology) 030304 developmental biology |
| Zdroj: | Nature chemical biology |
| ISSN: | 1552-4469 1552-4450 |
| Popis: | RNA modification in the form of N6-methyladenosine (m6A) regulates nearly all the post-transcriptional processes. The asymmetric m6A deposition suggests that regional methylation may have distinct functional consequences. However, current RNA biology tools do not distinguish the contribution of individual m6A modifications. Here we report the development of “m6A editing”, a powerful approach that enables m6A installation and erasure from cellular RNAs without changing the primary sequence. We engineered fusions of CRISPR-Cas9 and a single chain m6A methyltransferase that can be programmed with a guide RNA. The resultant m6A “writers” allow functional comparison of single site methylation in different mRNA regions. We further engineered m6A “erasers” by fusing CRISPR-Cas9 with ALKBH5 or FTO to achieve site-specific demethylation of RNAs. The development of programmable m6A editing not only expands the scope of RNA engineering, but also facilitates mechanistic understanding of epitranscriptome. Graphical Abstract Reporting Summary Further information on research design is available in the Nature Research Reporting Summary linked to this article. |
| Databáze: | OpenAIRE |
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