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Status |
Public on Sep 15, 2016 |
Title |
YTHDF3 facilitates translation and decay of the N6-methyladenosine-modified RNA |
Organism |
Homo sapiens |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing Other
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Summary |
N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic messenger RNAs (mRNAs), and plays important roles in cell differentiation and organism development. It regulates multiple steps throughout the RNA life cycle including RNA processing, translation, and metabolism, via the recognition by selective binding proteins. In cytoplasm, m6A binding protein YTHDF1 facilitates translation of m6A-modified mRNAs, and YTHDF2 accelerates the decay of m6A-modified transcripts. The biological function of YTHDF3, another cytoplasmic m6A binder of the YTH domain family, remains unknown. Here, we report that YTHDF3 promotes protein synthesis in synergy with YTHDF1, and affects methylated mRNA decay mediated by YTHDF2. Cells deficient in all of YTHDF proteins experience the most dramatic accumulation of the m6A-methylated transcripts. These results indicate that in cytoplasm, YTHDF proteins act in an integrated and cooperative network to accelerate metabolism of m6A-modified mRNAs. The combinative and dynamic nature of YTHDF proteins may collectively impact fundamental biological processes and diseases related to m6A RNA methylation.
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Overall design |
We utilized PAR-CLIP triplicates and RIP replicates to identify binding sites and target transcripts of YTHDF3, and performed ribosome profling replicates to assess the consequences of YTHDF3 siRNA knock-down in HeLa cells.
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Contributor(s) |
Shi H, Wang X, Lu Z, Zhao BS, Ma H, Hsu PJ, He C |
Citation(s) |
28106072 |
NIH grant(s) |
Grant ID |
Grant title |
Affiliation |
Name |
R01 GM071440 |
Direct Oxidative Nucleic Acids Demethylation: Chemistry and Mechanism of Direct DNA Repair Proteins |
UNIVERSITY OF CHICAGO |
HE |
R01 GM113194 |
Recognition and mechanism of N6-methyl adenosine modifications |
UNIVERSITY OF CHICAGO |
HE |
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Submission date |
Aug 30, 2016 |
Last update date |
May 15, 2019 |
Contact name |
Chuan He |
E-mail(s) |
chuanhe@uchicago.edu
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Phone |
773-702-5061
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Organization name |
The University of Chicago
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Department |
Department of Chemistry
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Street address |
929 E 57th St., GCIS E319
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City |
Chicago |
State/province |
ILLINOIS |
ZIP/Postal code |
60637 |
Country |
USA |
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Platforms (2) |
GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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Samples (25)
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Relations |
BioProject |
PRJNA340948 |
SRA |
SRP083699 |