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Small RNA sequencing revealed dysregulated piRNAs in Alzheimer's disease and their probable role in pathogenesis. Jyoti Roy, Prof. Bibekanand Mallick, Department of Life Science.
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P IWI-interacting RNAs (piRNAs), ∼23-36 nucleotide-long small non-coding RNAs, earlier believed to be germline-specific, have now been identified in somatic cells including neural cells. However, piRNAs have not yet been studied in the human brain (HB) and Alzheimer's disease (AD)-affected brain.
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In this study, by next-generation small RNA sequencing, 564 and 451 piRNAs
were identified in the HB and AD-affected brain respectively. The majority of the neuronal
piRNAs have intronic origin wherein primary piRNAs are mostly from the negative strand. piRNAs
originating from the coding sequence of mRNAs and tRNAs are highly conserved compared to other
genomic contexts. We found 1923 mRNAs significantly down-regulated in AD as the predicted targets of
125 up-regulated piRNAs. The filtering of targets based on our criteria coupled with pathway enrichment
analysis of all the predicted targets resulted in five most significant AD-associated pathways enriched with
four genes (CYCS, LIN7C, KPNA6, and RAB11A) found to be regulated by four piRNAs. The qRT-PCR study verified the
reciprocal expression of piRNAs and their targets. This study provides the first evidence of piRNAs in the HB and
AD which will provide the foundation for future studies to unravel the regulatory role of piRNAs in the human brain
and associated diseases. The sequencing data have been submitted to the GEO database
More in Molecular Biosystems (2017) Jan 27
(DOI: 10.1039/c6mb00699j)
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