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Computational Molecular Biology 2014, Vol. 4, No. 5
http://cmb.biopublisher.ca
2
Long non-coding RNAs (lncRNAs) are ncRNAs that
are longer than 200 nt and are abundant in brain cell
types (Mercer et al., 2008). The classical lncRNAs are
transcribed through the same transcriptional
machinery as other mRNAs, that is, RNA polymerase
II (PolII) occupancy in lncRNA promoter and active
histone modifications that are associated with lncRNA
promoter and gene body (Ilott and Ponting, 2013). The
number of all lncRNAs in mouse is estimated as at
least 40,000, which is more than the number of
protein-coding genes (Managadze et al., 2013). Most
lncRNAs are poorly annotated, and their functions
including the roles in CNS functions have not been
widely studied. The functions of lncRNAs appear to
associate with the genomic localization. For example,
lncRNAs can be in close with development associated
key genes. Neighboring protein-coding genes can
exhibit concordant or discordant expression patterns
with lncRNAs (Dinger et al., 2008; Ponjavic et al.,
2009), implying the potentially regulatory roles of
lncRNAs. Given most of lncRNAs are specifically
expressed in brain, the tissue specificity and brain
region specificity of lncRNAs seems to be
exceptionally vital for regulating CNS functions
(Mercer et al., 2008).
Some lncRNAs can regulate the epigenetic
modifications of protein-coding genes by cis- or
trans-acting fashions that need recruiting chromatin
remodeling factors to particular genomic loci (Khalil
et al., 2009; Redrup et al., 2009). One classical
example of this kind is the HOXC loci where a
lncRNA HOTAIR is transcribed and HOTAIR recruits
Polycomb protein complex PRC2 to HOXD loci and
represses HOXD in trans (Rinn et al., 2007).
1 lncRNAs in the central nervous system
The proximity of lncRNAs to genes related to
regulatory development proteins implies that lncRNAs
can play important roles in mammalian organ
development. Actually, many transcriptomic studies
have revealed the dynamic lncRNA expression
profiles and their functions among developing, fetal
and adult tissues, in additional to embryonic stem (ES)
cells (Dinger et al., 2008; Sheik Mohamed et al.,
2010), neural cell subtypes (Mercer et al., 2010; Aprea
et al., 2013; Lin et al., 2011), and brain (Mercer et al.,
2008; Ponjavic et al., 2009; Lv et al., 2013a; Lv et al.,
2013b).
1.1 lncRNA expression in brain and neural
differentiation
To quickly explore the brain developmental stage
specificity and brain specificity, the Allen Brain Atlas
(
http://www.brain-map.org/
) is an option. The Allen
Brain Atlas covers in situ hybridization (ISH) data and
is a constantly updating website, from which we are
able to examine the expression of hundreds of
lncRNAs in various tissues in adult and developing
mouse brains (Ng et al., 2012a). ~ 64% of 1328
lncRNAs investigated by Allen Brain Atlas are
detectable in adult mouse brain and are expressed
selectively for specific brain regions especially in
hippocampus and cerebellum (Mercer et al., 2008).
The brain region specificity is expected as the
expression is low in whole brain transcriptome
profiling. Therefore, it is necessary to perform
transcriptome studies on specific brain regions to
improve the lncRNA detection power. In addition, in
situ hybridization maps in Allen Brain Atlas revealed
that the most lncRNA are expressed in CNS (Mercer
et al., 2008). The lncRNAs expressed in CNS are
complex, including imprinted transcripts, cis-antisense,
intronic and bidirectional transcripts (Carninci et al.,
2005). Furthermore, many lncRNAs expressed in
CNS exhibited cross-species conservation, which is
meaningful as conservation may indicate functionality.
Ponjavic et al. have found over 200 lncRNAs that are
detectable in developing and adult brain (Ponjavic et
al., 2009), which are mainly located near
transcriptional regulators with similar expression
patterns and a large more conserved lncRNAs may
await to be discovered in near future.
Particular lncRNAs which are differentially expressed
during CNS differentiation are potential regulators in
mediating neural functions.
Sox2
, an important
transcription factor in ES cells, is necessary for neural
development. One study has demonstrated that
Sox2OT
, a lncRNA containing Sox2 in its introns, is
expressed in adult neurogenesis (Mercer et al., 2008).
Another report indicated that
Sox2OT
might be
responsible for modulating
Sox2
expression (Amaral
et al., 2009). Taken together, current evidences may