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Page 163 Kamal et al. J Transl Genet Genom 2024;8:162-85 https://dx.doi.org/10.20517/jtgg.2023.55

transcribed, meaning that most of the human transcribed RNAs consist of non-coding RNAs (ncRNAs),
[1]
genes that are transcribed into RNA but not translated into proteins . According to their size, the ncRNAs
[3]
are divided into two groups: small ncRNAs (< 200 nt) and long ncRNAs (LncRNAs) . The category of
small ncRNAs encompasses a diverse range of RNA types, including microRNAs, piwiRNAs, small
nucleolar RNAs , and small interfering RNAs (siRNAs) . lncRNAs are a class of RNA transcripts that are
[4]
[5]
[6]
long (i.e., more than 200 nucleotides) and not translated into proteins .
Small ncRNAs have been the subject of extensive research for a long time due to their significant functions
in the initiation and prognosis of many diseases. On the other hand, lncRNAs are not well understood
compared to other classes of ncRNAs , despite the fact that lncRNAs account for more than 80% of
[5]
ncRNAs . LncRNAs often exhibit low expression levels and are typically associated with specific tissues or
[2]
cell types . They have been growing as new contributors to cancer in both oncogenic and tumor
[7]
[8]
suppressive pathways . They have also recently been identified as significant players in both regular cellular
functions and disease development . Additionally, lncRNAs are crucial in numerous physiological
[9]
processes, including RNA splicing and X-chromosome inactivation .
[10]
CLASSIFICATION
The classification of lncRNAs, based on both their transcriptional orientation and their proximity to
adjacent protein-coding genes, encompasses four main types: Intergenic, Bidirectional, Antisense, and Sense
lncRNAs. Intergenic lncRNAs hold a significant position within human lncRNAs, constituting the largest
[11]
subgroup. Positioned in genomic regions without protein-coding sequences within a five-kilobase range ,
intergenic lncRNAs act as genomic separators between two protein-coding genes . Bidirectional lncRNAs,
[5]
another distinct type, are transcribed from the promoter of protein-coding genes but in the opposite
[5]
[12]
direction . Antisense lncRNAs form the second most prevalent group in humans . They are transcribed
from the antisense strand of protein-coding genes, often overlapping with exonic or intronic regions.
Finally, Sense lncRNAs, a unique category, originate from the sense strand of protein-coding genes. This
type includes instances where the lncRNA either partially overlaps with the gene, including portions of
exons, or entirely encompasses the gene's sequence within an intron . This diverse classification is depicted
[4]
in Figure 1.

FUNCTION
The functions of lncRNAs, like protein-coding genes, are diverse and vary greatly . LncRNAs have been
[1]
found to play a role in various significant biological processes via their interaction with DNA or chromatin,
their effect on regulatory or signaling pathways, and their regulatory function over other types of RNAs .
[5]
LncRNAs may function as decoys that can attract and prevent effector proteins from carrying out their
functions via binding and diverting them from their intended target site . Some lncRNAs can have
[6]
microRNA response elements, which are complementary sites for microRNAs. These are called competitive
endogenous RNAs, acting as molecular sponges for microRNAs, inhibiting them from reaching the target
genes of interest .
[11]

LncRNAs have several ways to regulate gene expression, with the most frequent being an epigenetic process
that frequently causes transcriptional suppression through interactions with chromatin-remodeling
[1]
proteins . LncRNAs, when attached to the chromatin, can regulate the expression of the genes by either
adjusting the local chromatin structure at these loci or by directing the regulatory molecules . cis-lncRNAs
[5]
(cis-acting lncRNAs), through transcriptional interference or via the modification of the chromatin,
regulate gene expression in the close genomic vicinity, whereas trans-lncRNAs (i.e., trans-acting lncRNAs)
[4]
regulate gene expression in distant genomic locations . LncRNAs can also contain specific domains for