Non-coding RNA networks underlying cognitive disorders across the lifespan

doi:10.1016/j.molmed.2011.02.002

Trends in Molecular Medicine

Volume 17, Issue 6, June 2011, Pages 337-346

https://doi.org/10.1016/j.molmed.2011.02.002 Get rights and content

Non-coding RNAs (ncRNAs) and their associated regulatory networks are increasingly being implicated in mediating a complex repertoire of neurobiological functions. Cognitive and behavioral processes are proving to be no exception. In this review, we discuss the emergence of many novel, diverse and rapidly expanding classes and subclasses of short and long ncRNAs. We briefly review the life cycles and molecular functions of these ncRNAs. We also examine how ncRNA circuitry mediates brain development, plasticity, stress responses and aging, and highlight its potential roles in the pathophysiology of cognitive disorders, including neural developmental and age-associated neurodegenerative diseases, as well as those that manifest throughout the lifespan.

Section snippets

Introduction to non-coding RNAs

Cognitive and behavioral dysfunction often arises when the integrity of brain form and function is compromised because of genetic and/or acquired etiological factors. It can manifest during any developmental stage and in adult life and can be associated with a very broad range of neurological and psychiatric conditions, from neural developmental disorders and age-associated neurodegenerative diseases to those occurring at different stages of life. In fact, cognitive and behavioral disorders

Life cycles and molecular functions of non-coding RNAs

Here we describe the recent emergence of diverse classes of short and long ncRNAs including their biogenesis, functional diversification via post-transcriptional mechanisms (e.g. RNA editing), RNP formation and intracellular and intercellular transport. We further highlight their roles in transcriptional, post-transcriptional and epigenetic, regulatory processes, such as X chromosome inactivation and genomic imprinting; nuclear subdomain formation; translational control; and modulation of

Central nervous system processes mediated by non-coding RNAs

ncRNAs are implicated in promoting neural stem cell (NSC) maintenance and maturation, including neurogenesis and gliogenesis 28, 89. These processes are crucial during development, and adult hippocampal neurogenesis is also involved in learning and memory [90]. One interesting ncRNA that regulates adult hippocampal neurogenesis is the small modulatory double-stranded RNA derived from the genomic NRSE/RE1 sequence, dsNRSE. This motif is bound by RE1-silencing transcription factor (REST), which

Concluding remarks

The life cycles, molecular functions, and biophysical and other features of ncRNA molecules seem to imbue ncRNA regulatory networks with the operational capacity, modularity, flexibility and environmental responsiveness, robustness and evolvability necessary for orchestrating higher-order CNS processes including emergent cognitive and behavioral functions. In this review, we examined how ncRNAs mediate CNS functions, from neural development and aging to plasticity and stress responses, by

Acknowledgments

We regret that space constraints have prevented the citation of many relevant and important references. M.F.M. is supported by grants from the National Institutes of Health (NS38902, MH66290, NS071571), as well as by the Roslyn and Leslie Goldstein, Harold and Isabel Feld, Mildred and Bernard H. Kayden, F.M. Kirby and Alpern Family Foundations.

Glossary

Chromatin: genomic DNA wrapped around histone protein octamers (i.e. nucleosomes), non-histone proteins and associated factors forming a compact ‘beads-on-a-string’ structure that is dynamically rearranged within the cell nucleus in an environmentally responsive manner.
Chromatin remodeling complexes: macromolecular assemblies of enzymes and associated factors that read, write and execute chromatin regulatory programs such as post-translational modifications of histone proteins, repositioning of

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Trends in Molecular Medicine

ReviewNon-coding RNA networks underlying cognitive disorders across the lifespan

Section snippets

Introduction to non-coding RNAs

Life cycles and molecular functions of non-coding RNAs

Central nervous system processes mediated by non-coding RNAs

Concluding remarks

Acknowledgments

Glossary

Noncoding RNAs and RNA editing in brain development, functional diversification, and neurological disease

Physiol. Rev.

Epigenetic principles and mechanisms underlying nervous system functions in health and disease

Prog. Neurobiol.

RNA editing, DNA recoding and the evolution of human cognition

Trends Neurosci.

Noncoding RNAs in long-term memory formation

Neuroscientist

Computational methodologies for studying non-coding RNAs relevant to central nervous system function and dysfunction

Brain Res.

deepBase: a database for deeply annotating and mining deep sequencing data

Nucleic Acids Res.

Specific expression of long noncoding RNAs in the mouse brain

Proc. Natl. Acad. Sci. U.S.A.

Genomic and transcriptional co-localization of protein-coding and long non-coding RNA pairs in the developing brain

PLoS Genet.

Long noncoding RNAs in neuronal-glial fate specification and oligodendrocyte lineage maturation

BMC Neurosci.

Identification of dynamically regulated microRNA and mRNA networks in developing oligodendrocytes

J. Neurosci.

Regulation of microRNA expression by induction of bidirectional synaptic plasticity

J. Mol. Neurosci.

Identification and quantitative analyses of microRNAs located in the distal axons of sympathetic neurons

RNA

RNAs as extracellular signaling molecules

J. Mol. Endocrinol.

RNA regulation of epigenetic processes

Bioessays

The prevalence of epigenetic mechanisms in the regulation of cognitive functions and behaviour

Curr. Opin. Neurobiol.

MicroRNAs and the advent of vertebrate morphological complexity

Proc. Natl. Acad. Sci. U.S.A.

The relationship between non-protein-coding DNA and eukaryotic complexity

Bioessays

Contrasts between adaptive coding and noncoding changes during human evolution

Proc. Natl. Acad. Sci. U.S.A.

An RNA gene expressed during cortical development evolved rapidly in humans

Nature

Epigenetic aberration of the human REELIN gene in psychiatric disorders

Mol. Psychiatry

The widespread regulation of microRNA biogenesis, function and decay

Nat. Rev. Genet.

Endogenous small interfering RNAs in animals

Nat. Rev. Mol. Cell Biol.

L1 retrotransposition in human neural progenitor cells

Nature

L1 retrotransposition in neurons is modulated by MeCP2

Nature

Comparative analysis of argonaute-dependent small RNA pathways in Drosophila

Mol. Cell

Common themes in siRNA-mediated epigenetic silencing pathways

Int. J. Dev. Biol.

The snoRNA HBII-52 regulates alternative splicing of the serotonin receptor 2C

Science

Long non-coding RNAs in nervous system function and disease

Brain Res.

Long noncoding RNAs with enhancer-like function in human cells

Cell

RNA maps reveal new RNA classes and a possible function for pervasive transcription

Science

Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project

Nature

The transcriptional landscape of the mammalian genome

Science

Antisense transcription in the mammalian transcriptome

Science

Nuclear-localized tiny RNAs are associated with transcription initiation and splice sites in metazoans

Nat. Struct. Mol. Biol.

Evolution, biogenesis and function of promoter-associated RNAs

Cell Cycle

Exosome complex and pervasive transcription in eukaryotic genomes

Review
Non-coding RNA networks underlying cognitive disorders across the lifespan