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Transfer RNA‐derived fragments: origins, processing, and functions

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Abstract Deep sequencing approaches have revealed multiple types of small RNAs with known and unknown functions. In this review we focus on a recently identified group of small RNAs that are derived from transfer RNAs (tRNAs), tRNA fragments (tRFs). We review the mechanism of their processing and their functions in mammalian cells, and highlight points of possible cross‐talk between tRFs and the canonical small RNA pathway characterized by small interfering RNAs (siRNAs), microRNAs (miRNAs), and Piwi‐interacting RNAs (piRNAs). We also propose a nomenclature that is based on their processing characteristics. WIREs RNA 2011 2 853–862 DOI: 10.1002/wrna.96 This article is categorized under: RNA Processing > tRNA Processing Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs

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Proposed nomenclature of small (less than 30 nt) tRFs. 3′U transfer RNA‐derived fragments (tRFs) are processed from pre‐tRNAs and consist of the sequence between the RNase Z cleavage site and the PolIII run‐off poly(U) tract. Mature tRNAs can generate two types of tRFs: one is processed from the 5′end (5′ tRFs) and one from the 3′end that contains the added CCA sequence (3′ CCA tRFs).

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Possible processing and maturation of transfer‐RNA‐derived fragments (tRFs). 3′ U tRFs could be processed from pre‐tRNAs by RNase Z and promptly exported into the cytoplasm where they incorporate into Argonaute complexes. Alternatively, pre‐tRNAs may go through premature rapid nuclear export and be processed by a cytoplasmic RNase. tRNA processed by RNAse P and Z with the 3′ terminal CCA added may be prematurely exported into the cytoplasm and a lack of base modifications may cause them to form a Dicer accessible structure. Alternatively, mature aminoacylated tRNAs may enter the small RNA pathway via Dicer processing. Dicer could produce two types of tRFs from these tRNAs: 5′tRFs and 3′CCA tRFs. 3′ CCA tRFs can incorporate into Argonaute proteins. Open triangle: RNAse Z cleavage site; filled triangle: RNase P cleavage site. Red arrows denote possible premature nuclear export.

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