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The search for endogenous siRNAs in the mammalian brain.

ABSTRACT: A decade ago, RNA interference was proposed to serve as a physiologic means of regulating long-term gene expression in the mammalian brain. However, during the intervening years, this hypothesis appeared to be contradicted by both experimental data and theoretical considerations. More recently, the advent of deep sequencing technology has permitted a re-assessment of this issue. As reviewed here, a large population of small RNAs having features characteristic of endogenous siRNAs are detected within adult mouse hippocampus, which derive from genes involved in synaptic structure and signaling, and which show a significant, though modest (16-22%) up-regulation during olfactory discrimination training. Small RNAs derived from abundant cellular noncoding RNAs are also detected; in particular, a subpopulation of RNAs 25-30 nt. in length shows very large (>100 fold) up-regulation during olfactory discrimination training. Preliminary data suggest that the 25-30 nt. RNAs may associate with MIWI rather than Argonaute 1-4 homologues. I conclude that, despite their apparent low abundance, endogenous siRNAs and noncoding RNA-derived small RNAs are likely to play an important role in regulating synaptic plasticity.

SUBMITTER: Smalheiser NR

PROVIDER: S-EPMC3291744 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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The search for endogenous siRNAs in the mammalian brain.

Smalheiser Neil R NR

Experimental neurology 20111028 2

A decade ago, RNA interference was proposed to serve as a physiologic means of regulating long-term gene expression in the mammalian brain. However, during the intervening years, this hypothesis appeared to be contradicted by both experimental data and theoretical considerations. More recently, the advent of deep sequencing technology has permitted a re-assessment of this issue. As reviewed here, a large population of small RNAs having features characteristic of endogenous siRNAs are detected wi ...[more]

PMID: 22062046

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Project description:BackgroundSmall endogenous non-coding RNAs (sncRNAs) such as small interfering RNA (siRNA), microRNA and other small RNA transcripts are derived from distinct loci in the genome and play critical roles in RNA-mediated gene silencing mechanisms in plants and metazoa. They are approximately 22 nucleotides long; regulate mRNA stability through perfect or imperfect match to the targets. The biological activities of sncRNAs have been related to many biological events, from resistance to microbe infections to cellular differentiation. The development of the zoonotic parasite Schistosoma japonicum parasite includes multiple steps of morphological alterations and biological differentiations, which provide a unique model for studies on the functions of small RNAs. Characterization of the genome-wide transcription of the sncRNAs will be a major step in understanding of the parasite biology. The objective of this study is to investigate the transcriptional profile and potential function of the small non-coding RNAs in the development of S. japanicum.ResultsThe endogenous siRNAs were found mainly derived from transposable elements (TE) or transposons and the natural antisense transcripts (NAT). In contrast to other organisms, the TE-derived siRNAs in S. japonicum were more predominant than other sncRNAs including microRNAs (miRNAs). Further, there were distinct length and 3'end variations in the sncRNAs, which were associated with the developmental differentiation of the parasite. Among the identified miRNA transcripts, there were 38 unique to S. japonicum and 16 that belonged to 13 miRNA families are common to other metazoan lineages. These miRNAs were either ubiquitously expressed, or they exhibited specific expression patterns related to the developmental stages or sex. Genes that encoded miRNAs are mainly located in clusters within the genome of S. japonicum. However, genes within one cluster could be differentially transcribed, which suggested that individual genes might be regulated by distinct mechanisms during parasite development.ConclusionsMany miRNA and endogenous siRNA transcripts were identified in S. japonicum and the amount of siRNA was at least 4.4 and 1.6 times more than that of miRNA in both schistosomulum and adult worm stages respectively. SiRNAs are mainly derived from transposable elements (or transposons); while natural antisense transcripts (NAT)-derived siRNAs were much less. A majority of miRNA transcripts identified in the parasite were species-specific and the expression of certain miRNAs was found developmentally regulated. Both miRNA and siRNAs are potentially important regulators in the development of schistosomal parasites.

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The search for endogenous siRNAs in the mammalian brain.

Publications

The search for endogenous siRNAs in the mammalian brain.

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