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bioRxiv · 10.1101/2021.04.26.441477

A pro-metastatic tRNA fragment drives Nucleolin oligomerization and stabilization of bound metabolic mRNAs

Liu, X.·Alwaseem, H.·Molina, H.·Tavora, B.·Tavazoie, S.
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Abstract

Stress-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 Nucleolins 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.

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Liu, X., Alwaseem, H., Molina, H., Tavora, B., Tavazoie, S.. 2021-04-26. A pro-metastatic tRNA fragment drives Nucleolin oligomerization and stabilization of bound metabolic mRNAs. https://doi.org/10.1101/2021.04.26.441477

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