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Computational Molecular Biology 2014, Vol. 4, No. 5
http://cmb.biopublisher.ca
3
suggest that lncRNAs can mediate the expression of
other factors to orchestrate neural cell identity.
RNA
sequencing
(RNA-seq)
followed
by
computational analysis has been widely used to
identify tissue restricted expressed lncRNAs. Kaushik
et al. had used this approach to identify lncRNA
transcripts from five different tissues of adult
zebrafish (Kaushik et al., 2013). They identified 442
predicted lncRNA transcripts and 77 differentially
expressed lncRNAs. Within the differentially
expressed lncRNAs, 61% are brain restricted
expressed.
1.2 High-throughput approaches to study the
lncRNAs in CNS development.
A study systematically found more than 1600
conserved lincRNAs in four mouse cell types based
on chromatin signatures (Guttman et al., 2009). The
cell types they investigated include neural precursor
cells (NPCs). Their analysis found that those lncRNAs
that are associated with “brain cluster” are related to
some brain related biological processes, such as
hippocampal development and oligodendrocyte (OL)
myelination.
The results together with others (Lv et al., 2013a; Lv
et al., 2013b; Ng et al., 2012b; Qureshi and Mehler,
2012) have highlighted the importance of lncRNAs in
regulation of cellular fate in neural cells and brain.
Increasing evidences suggested that lncRNAs can
control epigenetic targeting via their ability to bind
RNA, DNA and protein (Guttman and Rinn, 2012;
Mercer and Mattick, 2013; Tsai et al., 2010). lncRNAs
contain functional three-dimensional structures that
can form scaffolds or molecular ‘sponges’ and in turn
allow activity-dependent regulation (Tripathi et al.,
2010; Mercer and Mattick, 2013; Tsai et al., 2010;
Barry et al., 2013).
Malat1
, as an example, has been
shown to relate with synapse formation by acting as
splicing factor ‘sponge’, suggested that lncRNAs have
alternative splicing functions in neural cells (Anko
and Neugebauer, 2010). As an earlier mechanistic
study, a lncRNA related to alternative splicing in
neuronal cells was reported for Gomafu (Barry et al.,
2013). The expression of
Malat1
was generally stable
during induction of stimulating neurons, implying that
Malat1
plays a different role in human neuronal
functions, or perhaps has regulatory functions in
distinct subtypes of neural cells. In addition, lncRNAs
are also associated with mRNA transcription,
translation and decay (Tripathi et al., 2013; Mercer
and Mattick, 2013). Altogether, the enormous
regulatory potentials of investigated lncRNAs and
even more candidates would call for more detailed
studies about the distinct group of non-coding RNAs.
The differential lncRNA expression patterns should be
interpreted by experimental or computational
functional analysis. As a first step, Mercer et al.
(Mercer et al., 2010) systematically analyzed
lncRNAs that had significant changes in expression
and found that several of these lncRNAs were part of
or close to protein-coding gene loci with a known
function in brain and CNS development. In addition, a
software Scripture was used to reconstruct the
transcriptome of mouse ES cells, neuronal precursor
(NP) cells and lung fibroblast cells. The full-length
transcript structures for most annotated genes and a
large number of lncRNAs were construct (Guttman et
al., 2010). Another study found that there were ~170
lncRNAs that are differentially expressed during
lineage commitment of neuron and oligodendrocyte
(OL), neuronal-glial transitions, and developmental
stages of OL (Mercer et al., 2010). Recently, a study
used RNA-seq to identify lncRNAs that may be
important in neurogenic commitment process (Aprea
et al., 2013). Some selected lncRNAs have been
validated. Recently, Ramos et al. utilized high-
throughput approaches including RNA-seq and
ChIP-seq to identify lncRNAs related to distinct
neural cell types and lncRNAs having important roles
in embryonic and adult neurogenesis (Ramos et al.,
2013).
In addition, more and more lncRNAs were associated
with conserved enhancer elements that regulate the
brain development. p300 and H3K4me1 marks have
been employed in one work to identify enhancers in
mouse that are mediated by neuronal activity (Kim et
al., 2010). These predicted enhancers are rich in
putative lncRNAs, expanding in either direction from
the CBP binding positions and within 2000 bp from