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Characterization of transcription termination-associated RNAs: new insights into their biogenesis, tailing, and expression in primary tumors

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Item Type:Article
Title:Characterization of transcription termination-associated RNAs: new insights into their biogenesis, tailing, and expression in primary tumors
Creators Name:Laudadio, I. and Formichetti, S. and Gioiosa, S. and Klironomos, F. and Rajewsky, N. and Macino, G. and Carissimi, C. and Fulci, V.
Abstract:Next-generation sequencing has uncovered novel classes of small RNAs (sRNAs) in eukaryotes, in addition to the well-known miRNAs, siRNAs, and piRNAs. In particular, sRNA species arise from transcription start sites (TSSs) and the transcription termination sites (TTSs) of genes. However, a detailed characterization of these new classes of sRNAs is still lacking. Here, we present a comprehensive study of sRNAs derived from TTSs of expressed genes (TTSa-RNAs) in human cell lines and primary tissues. Taking advantage of sRNA-sequencing, we show that TTSa-RNAs are present in the nuclei of human cells, are loaded onto both AGO1 and AGO2, and their biogenesis does not require DICER and AGO2 endonucleolytic activity. TTSa-RNAs display a strong bias against a G residue in the first position at 5 end, a known feature of AGO-bound sRNAs, and a peculiar oligoA tail at 3 end. AGO-bound TTSa-RNAs derive from genes involved in cell cycle progression regulation and DNA integrity checkpoints. Finally, we provide evidence that TTSa-RNAs can be detected by sRNA-Seq in primary human tissue, and their expression increases in tumor samples as compared to nontumor tissues, suggesting that in the future, TTSa-RNAs might be explored as biomarker for diagnosis or prognosis of human malignancies.
Keywords:Noncoding RNAs, Argonaute Proteins, Start Sites, Disease, Dicer, Recognition, microRNAs, Framework, Elements, Complex
Source:International Journal of Genomics
ISSN:2314-436X
Publisher:Hindawi (U.S.A.)
Volume:2018
Page Range:1243858
Date:26 April 2018
Official Publication:https://doi.org/10.1155/2018/1243858
PubMed:View item in PubMed

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