It can be tough to find a significant other that checks all the boxes: smart, funny, and into epigenetics. But if you think your relationship is tough to figure out, just wait until you see the relationship between tRNA derived fragments and mRNAs. New research from the lab of Isidore Rigoutsos (Thomas Jefferson University, USA) reveals that cancer cell type, gene length, repeat elements, and even gender play a role in determining who pairs up with who.
tRNA-derived fragments (tRFs) are short (14-30 nt) RNA sequences formed via cleavage of either mitochondrial or nuclear tRNAs. While the functional significance of tRFs is still nebulous, they have been implicated in cell stress and cancer, and previous work from the Rigoutsos lab showed that tRFs can vary based on cancer subtype. Additionally, these molecules can bind with and alter the production of mRNAs.
To better understand the tRF-mRNA relationship in cancer, the group screened 32 cancer types from The Cancer Genome Atlas (TCGA) short RNA-seq dataset to uncover potential tRFs. Data mining of 10,274 TCGA samples revealed 20,722 tRFs that had significant expression in at least one of the 32 cancer types. Through some serious data crunching and statistical analysis, they investigated tRF-mRNA relationships in a multitude of contexts.
Here’s the speed dating version of their results:
- In the TCGA sample set, tRFs cleaved from mitochondrial tRNAs have higher proportional abundance, unique cleavage patterns, and different lengths when compared to those arising from nuclear tRNAs
- Although the same mRNAs and tRFs are present in different cancers, which mRNAs and tRFs interact is unique to each cancer type
- Many of the tRF-mRNA correlations and associated protein pathways are only enriched in one cancer type
- For pathways that are represented in multiple cancer types, the mRNA-tRF interactions are still unique
- In addition to cancer type specificity, the tRF-mRNA interactions also display a degree of tissue specificity and gender specificity
- Genes whose mRNAs participate in tRF interactions are more likely to be enriched in several families of repeated elements
- This correlation is stronger for mitochondrial tRFs than for nuclear tRFs
Senior author Isidore Rigoutsos noted that “… these tRF-mRNA associations could provide valuable insights for how to approach research into treatment because, they appear to be involved in a different relationship in every cancer.” The authors also note that “tRF production and the resulting cleavage profiles are the outcome of a currently unknown mechanism”, so there’s a lot more work to be done!
Make a date with the full paper in Cancer Research, April 2019.