| Autor: |
Bernardo Tavora, Xuhang Liu, Hanan Alwaseem, Henrik Molina, Sohail F. Tavazoie |
| Rok vydání: |
2021 |
| Předmět: |
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| Popis: |
SUMMARYStress-induced cleavage of transfer RNAs (tRNAs) into tRNA-derived fragments (tRFs) occurs across organisms from yeast to human, yet its mechanistic bases and pathological consequences remain poorly defined. By performing genome-wide small RNA profiling, we detected increased abundance of a Cysteine tRNA fragment (5’-tRFCys) during breast cancer metastatic progression. 5’’-tRFCys is required for efficient breast cancer metastatic lung colonization and metastatic cell survival. We identified Nucleolin as the direct binding partner of 5’-tRFCys. 5’-tRFCys binding enhanced the stability of Nucleolin’s associated pro-metastatic transcripts encoding metabolic enzymes Mthfd1l and Pafah1b1. 5’-tRFCys stabilized these transcripts by promoting Nucleolin oligomerization and the assembly of Nucleolin and its bound transcripts into a higher-order ribonucleoprotein complex. Our findings reveal that a tRF can promote oligomerization of an RNA binding protein into a stabilizing ribonucleoprotein complex containing specific target transcripts, thereby driving specific metabolic pathways underlying cancer progression. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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