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Characterization of Transcription Termination-Associated RNAs: New Insights into
their Biogenesis, Tailing, and Expression in Primary Tumors
#MMPMID29854718
Laudadio I
; Formichetti S
; Gioiosa S
; Klironomos F
; Rajewsky N
; Macino G
; Carissimi C
; Fulci V
Int J Genomics
2018[]; 2018
(?): 1243858
PMID29854718
show ga
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.