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| Status |
Public on Aug 08, 2023 |
| Title |
METTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancer |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Non-coding RNA profiling by high throughput sequencing
Other
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| Summary |
Newly growing evidence highlights the essential role that epitranscriptomic marks play in the development of cancer; however, little is known about the role and implications of altered epitranscriptome deposition in prostate cancer. Here, we show that the transfer RNA N7-methylguanosine (m7G) transferase METTL1 is highly expressed in primary and advanced prostate tumours. Mechanistically, we find that METTL1 depletion causes the loss of m7G tRNA methylation and promotes the biogenesis of a novel class of small non-coding RNAs derived from 5’tRNA fragments. 5′ tRNA-derived small RNAs steer translation control to favour the synthesis of key regulators of tumour growth suppression, interferon pathway, and immune effectors. Knockdown of Mettl1 in prostate cancer preclinical models increases intratumoural infiltration of pro-inflammatory immune cells and enhances responses to immunotherapy, leading to decreased tumour progression. Collectively, our findings reveal a therapeutically actionable role of METTL1-directed m7G tRNA methylation in cancer cell translational control and tumour biology.
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| Overall design |
Sequences of RNAs bound to METTL1 in prostate cancer cell lines PC3. Photoactivatable-ribonucleoside-enhanced cross-linking immunoprecipitation (PAR-CLIP) was applied to PC3 cells expressing HA-METTL1.Empty vector was used as control. METTL1 was IP using anti-HA antibodies. RNAs bound to METTL1 were extracted and sequenced.
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| Contributor(s) |
Blanco S, Merkel A, Guil S |
| Citation(s) |
37516825 |
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| Submission date |
Apr 26, 2023 |
| Last update date |
Aug 08, 2023 |
| Contact name |
Ana Maria Aransay |
| E-mail(s) |
amaransay@cicbiogune.es
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| Phone |
0034944061325
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| Organization name |
CIC bioGUNE
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| Department |
Genome Analysis Platform
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| Street address |
Parque tecnologico de Bizkaia, Building 801-A
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| City |
Derio |
| State/province |
BIZKAIA |
| ZIP/Postal code |
48160 |
| Country |
Spain |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA962138 |
