Small RNA sequencing revealed dysregulated piRNAs in Alzheimer's disease and their probable role in pathogenesis

Abstract

PIWI-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. 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 (Accession no. GSE85075).

Transcriptome-wide piRNA profiling in human brains of Alzheimer's disease

“…Two piRNAs, including DQ599147 at CTC1 (FC=1.8, p=0.048) and DQ597974 near C11orf87 (FC=2.0, p=0.031), expressed in significantly higher levels in cases than controls (Table S2) replicated previous findings (Roy, et al, 2017). …”

“…Across transcriptome, only 5 percent of piRNAs can be mapped to protein-coding genes (Brennecke, et al, 2007); however, among the AD-associated piRNAs identified in this study, 41% are enriched in the protein-coding genes, suggesting a strong correlation among these genes, piRNAs and AD. Sequences of the AD-associated piRNAs are complement to or close to these protein-coding genes, and thus, the piRNAs are most likely to target and regulate these nearest genes by sequence complementarity (Roy, et al, 2017). …”

Investigating piwi‐interacting RNA regulome in human neuroblastoma

“…27,45 It is also observed that specific set of mRNAs are actively selected for piRNA production as a requirement for various regulatory purposes. 27,45 It is also observed that specific set of mRNAs are actively selected for piRNA production as a requirement for various regulatory purposes.…”

miR-429 inhibits metastasis by targeting KIAA0101 in Soft Tissue Sarcoma

“…The most developed treatment option includes surgical resection and adjuvant-chemotherapy to which they respond poorly, leading to local recurrence and distant metastasis. New treatment procedures like targeted therapies and development of diagnostic markers need to be augmented for tackling this early metastatic cancer possibly by harnessing the potential of small noncoding RNAs (ncRNAs) such as microRNAs (miRNAs) and piwiinteracting RNAs (piRNAs) [2][3][4][5].…”