Fragments of rRNA, mitochondrial transcripts, microRNAs, fragments of scRNAs, snRNA and snoRNA, fragments of several mRNAs as well as the set of newly discovered transcripts were found to be permanent representatives of human blood plasma RNAs. Advanced mapping allowed to identify circulating herpes virus and enterobacterial transcripts. Documented profile of circulating RNA of healthy individuals provides basis for development of new approaches in research and diagnosis of human pathology.
11% of the human genome is composed of Alu-retrotransposons, whose
transcription by RNA polymerase III (Pol III) leads to the accumulation of
several hundreds to thousands of Alu-RNA copies in the cytoplasm. Expression of
Alu-RNA Pol III is significantly increased at various levels of stress, and the
increase in the Alu-RNA level is accompanied by a suppression of proliferation,
a decrease in viability, and induction of apoptotic processes in human cells.
However, the question about the biological functions of Pol III
Alu-transcripts, as well as their mechanism of action, remains open. In this
work, analogues of Alu-RNA and its evolutionary ancestor, 7SL RNA, were
synthesized. Transfection of human breast adenocarcinoma MCF-7 cells with the
Alu-RNA and 7SL RNA analogues is accompanied by a decrease in viability and by
induction of proapoptotic changes in these cells. The analysis of the combined
action of these analogues and actinomycin D or tamoxifen revealed that the
decreased viability of MCF-7 cells transfected with Alu-RNA and 7SL RNA was due
to the modulation of transcription. A whole transcriptome analysis of gene
expression revealed that increased gene expression of the transcription
regulator NUPR1 (p8), as well as the transcription factor
DDIT3 (CHOP), occurs under the action of both the Alu- and 7SL
RNA analogues on MCF-7 cells. It has been concluded that induction of
proapoptotic changes in human cells under the influence of the Alu-RNA and 7SL
RNA analogues is related to the transcriptional activation of the genes of
cellular stress factors, including the endoplasmic reticulum stress response
factors.
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