期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 113, 期 45, 页码 12697-12702出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1609287113
关键词
piwi-interacting RNA; transposon; DNA methylation; behavior; endogenous siRNA
资金
- Howard Hughes Medical Institute (HHMI)
- NIH Grants [NS076465, MH083804, MH070596, CA155226, CA104348, CA143032]
- Foundation Grant STARR [I9-A9-071]
- Bert L. and N. Kuggie Vallee Foundation
- Irma T. Hirschl Charitable Trust
- Monique Weill-Caulier Charitable Trust
- Pershing Square Sohn Cancer Research Alliance
- NASA [NNX14AH50G, 15-15Omni2-0063]
- WorldQuant Foundation
- NIH Training Grant [1T32GM083937]
Piwi-interacting RNAs (piRNAs), long thought to be restricted to germline, have recently been discovered in neurons of Aplysia, 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 (Mili(-/-)) mice demonstrate that brain genomic DNA is preferentially hypomethylated within intergenic areas and LINE1 promoter areas of the genome. Furthermore, Mili 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 Aplysia may also have potential roles in the mammalian brain.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据