TitleRoles for small noncoding RNAs in silencing of retrotransposons in the mammalian brain.
Publication TypeJournal Article
Year of Publication2016
AuthorsNandi, Sayan, Chandramohan Dhruva, Fioriti Luana, Melnick Ari M., H├ębert Jean M., Mason Christopher E., Rajasethupathy Priyamvada, and Kandel Eric R.
JournalProc Natl Acad Sci U S A
Volume113
Issue45
Pagination12697-12702
Date Published2016 Nov 08
ISSN1091-6490
Abstract

<p>Piwi-interacting RNAs (piRNAs), long thought to be restricted to germline, have recently been discovered in neurons of , with a role in the epigenetic regulation of gene expression underlying long-term memory. We here ask whether piwi/piRNAs are also expressed and have functional roles in the mammalian brain. Large-scale RNA sequencing and subsequent analysis of protein expression revealed the presence in brain of several piRNA biogenesis factors including a mouse piwi (Mili), as well as small RNAs, albeit at low levels, resembling conserved piRNAs in mouse testes [primarily LINE1 (long interspersed nuclear element1) retrotransposon-derived]. Despite the seeming low expression of these putative piRNAs, single-base pair CpG methylation analyses across the genome of Mili/piRNA-deficient ( ) mice demonstrate that brain genomic DNA is preferentially hypomethylated within intergenic areas and LINE1 promoter areas of the genome. Furthermore, mutant mice exhibit behavioral deficits such as hyperactivity and reduced anxiety. These results suggest that putative piRNAs exist in mammalian brain, and similar to the role of piRNAs in testes, they may be involved in the silencing of retrotransposons, which in brain have critical roles in contributing to genomic heterogeneity underlying adaptation, stress response, and brain pathology. We also describe the presence of another class of small RNAs in the brain, with features of endogenous siRNAs, which may have taken over the role of invertebrate piRNAs in their capacity to target both transposons, as well as protein-coding genes. Thus, RNA interference through gene and retrotransposon silencing previously encountered in may also have potential roles in the mammalian brain.</p>

DOI10.1073/pnas.1609287113
Alternate JournalProc Natl Acad Sci U S A
PubMed ID27791114
PubMed Central IDPMC5111663
Grant ListR01 CA155226 / CA / NCI NIH HHS / United States
R56 CA104348 / CA / NCI NIH HHS / United States
T32 GM083937 / GM / NIGMS NIH HHS / United States
R01 MH070596 / MH / NIMH NIH HHS / United States
R01 MH083804 / MH / NIMH NIH HHS / United States
R01 NS076465 / NS / NINDS NIH HHS / United States
R01 CA104348 / CA / NCI NIH HHS / United States
R01 CA143032 / CA / NCI NIH HHS / United States