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Dissecting tRNA-derived fragment complexities using personalized transcriptomes reveals novel fragment classes and
Aristeidis G Telonis1, Phillipe Loher1, Shozo Honda1
1Computational Medicine Center, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA.
Oncotarget
|September 2, 2015
Summary
Human transfer RNA (tRNA) fragments exhibit distinct patterns influenced by genetics and environment. These tRNA fragments, including novel internal tRNA fragments (i-tRFs), show cell-dependent loading onto Argonaute, suggesting diverse biological roles.
Area of Science:
- Genomics
- Molecular Biology
- Biochemistry
Background:
- Transfer RNAs (tRNAs) are essential for protein synthesis.
- Emerging evidence suggests non-canonical roles for tRNA-derived fragments.
- Understanding tRNA fragment variability is crucial for deciphering their biological functions.
Purpose of the Study:
- To analyze the characteristics and variability of tRNA fragments across diverse human populations and disease states.
- To identify novel categories of tRNA fragments and their potential regulatory roles.
- To investigate the association of tRNA fragments with Argonaute proteins and the RNA interference pathway.
Main Methods:
- Transcriptomic data analysis of healthy individuals and breast cancer patients.
- Analysis of The Cancer Genome Atlas (TCGA) breast cancer samples.
- HITS-CLIP data analysis and experimental validation of specific tRNA fragments.
Main Results:
- Identified numerous constitutive tRNA fragments with quantized lengths and overlapping sequences across individuals.
- Demonstrated that tRNA fragment characteristics (length, abundance) are influenced by gender, population, race, tissue, and disease.
- Discovered a novel class of internal tRNA fragments (i-tRFs) that contribute to observed variations and are differentially abundant in breast cancer.
- Showed cell-dependent loading of tRNA fragments onto Argonaute, indicating potential roles in RNA interference.
Conclusions:
- tRNA fragments are highly variable and their characteristics are linked to biological and demographic factors.
- Internal tRNA fragments (i-tRFs) represent a significant class of regulatory molecules with potential roles in disease.
- The cell-dependent association of tRNA fragments with Argonaute suggests functional implications in gene regulation via the RNA interference pathway.
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