Different Types of RNA Molecule and Their Functional Role in Cell

Course: MCB303
Name: Noor-E-Khadiza Shama

ID: 1921168
Date: 11/08/21
Different types of RNA molecule and their functional

role in cell
Small nuclear RNA (snRNA)
Small nuclear RNAs are approximately 150 nucleotides long, single stranded RNA molecules
with extensive 2’O methylation and pseudouridylation. They are found in eukaryotic cells. They,
along with other proteins play critical role in pre-mRNA splicing during post transcriptional
modification of mRNA. In the process, the non-coding sequence which are called introns are
spliced and removed and coding regions called exons are reattached. (2)
In pre-mRNA splicing process, a complex consisting of five small nuclear RNAs (U1, U2, U4, U5
and U6) along with other proteins are formed. This complex is known as spliceosome which can
splice RNA in a stepwise process given below-
1. At first, the 5’-end of U1 snRNA recognize and binds to 5’ splice-site of pre-mRNA

by complementary base-pairing.
2. Then U2 snRNA attach to 3’ splice-site sequence of pre-mRNA which causes the
branch point nucleotide (adenosine) to bulge out.
3. Consequently, the other snRNAs- U4/U6 U5 tri-snRNP joins the complex.
4. This initiates a series of RNA-RNA rearrangement which consequently destabilize
the U1 and U4 from the complex.
5. This activates the spliceosome where the 2’OH group of the branch point attacks
the 5’SS and the intron is excised and released
6. Following which, the U2, U5 and U6 snRNPs are also released and a mature mRNA
is produced. (2)
The above five steps are illustrated by the figure below:
Figure 1 Steps of pre-mRNA splicing by snRNAs (1)
MicroRNA (miRNA)
MicroRNAs are 21-23 ribonucleotides long non-coding RNA which are present in eukaryotic
cells (6). They play major role in post-transcriptional gene regulation. Micro RNA is also known
to cause gene silencing and translational repression as well as activation. (3)
In the gene regulation mechanism, the miRNA binds to the 3’ UTR of the targeted mRNA which
in turn may cause translational repression, deadenylation and decapping of mRNA and cleavage
of mRNA.
In the mRNA cleavage process, extensive base-pairing occur between miRNA and mRNA which
forms RISC (RNA-induced silencing complex). Following which, Ago2 is recruited in the targeted
area in the RISC. Ago2 have slicer activity which means it can cleave RNA. The cleavage of
mRNA by Ago2 results in the nucleolytic degradation of the targeted mRNA. As a result, the
gene is not expressed and no protein can be produced. (14) This process is illustrated by the
following figure:
Figure 2 The cleavage of mRNA by Ago2 RISC. (14)
Small nucleolar RNA (snoRNA)

Small nucleolar RNAs are 60-300 nucleotides long non-coding RNAs. They are encoded by
introns and are found mainly in the nucleolus. They play major role in posttranscriptional
modification and cleavage of ribosomal RNAs, snRNA and other cellular RNAs. This modification
involves extensive methylation and pseudouridylation of rRNAs and snRNAs.
The small nucleolar RNAs are divided into 2 classes: C/D box snoRNAs and H/ACA box. (4) In the
C/D box snoRNA, there are 2 conserved sequences, which are: C box (RUGAUGA) and D box
(CUGA) located at the 5’ and 3’ ends respectively. These C and D boxes serves as methylation
guidelines. The H/ACA box contains 2 conserved sequences, which are: H box (ANANNA) and
ACA box (ACA). These H and ACA boxes serves as pseudouridylation guidelines. (4)(9)
One key role of snoRNA is the modification and maturation of rRNA and snRNA. The
modification involves methylation and pseudouridylation of rRNA and snRNA. In the
methylation process, the C/D box snoRNA and fibrillarin, which is a protein showing methyl
transferase activity is used. (9) At first, the sequence upstream of D box being complementary
to rRNA, attaches to it. Following this, the fibrillarin directs 2’-O-methylation in rRNA. (9) In the
pseudouridylation process, H/ACA snRNA along with dyskerin, which shows pseudouridine
synthase activity. At first, the H/ACA box snoRNA attaches with the targeted rRNA. Then
dyskerin carries out the isomerization of uridine into pseudouridine. (10)
The binding of snoRNA in 2' -O- methylation and pseudouridylation is illustrated by the
following figure:
Figure 3 The snoRNA guided methylation and pseudouridylation (7)
In addition to this, snoRNAs also carries out regulation of mRNA splicing and editing. (4)
long non-coding RNA (lncRNA)

Long non-coding RNAs are more than 200 nucleotides long RNAs which play vital role in gene
regulation. They can interact with DNA, RNA as well as protein and regulate chromatin
structure and function. LncRNAs can act as decoys, scaffolds, and enhancer RNAs.
In chromatin regulation, the negatively charged lncRNA binds to the positively charged histone
tails. This causes the histone to loosely pack with the DNA in chromatin and as a result, the
gene expression is switched on in the chromatin. (5)
LncRNA is also used as a decoy molecule. They work by blocking a certain biochemical route
by directly binding to some protein molecules, such as chromosomal folding proteins or
transcription regulators which inhibits their function.
LncRNAs can also bind directly to transcription regulators which in turn blocks transcription
factor. This together suppress the downstream gene transcription. LncRNA also acts as scaffold.
For example, an lncRNA called X-inactive specific transcript (Xist) RNA is encoded by the X
chromosome in female. This Xist RNA recruits two complex PRC1and PRC2, which suppress the
expression of X chromosome. Thus, in females, one chromosome remains inactivated. (16)
There are many IncRNA carrying out several different functions. Some of them are listed in the
table below (15):
Piwi-interacting RNAs (piRNA)

Piwi-interacting RNAs were first found in Drosophila testes in 2001. It is a type of non-coding
RNA which is 24 to 31 nucleotides long and are stabilized by piwi proteins. They are primarily
transcribed in germ line cells as well as somatic cells. (8)(12)
It plays a role in transcriptional gene silencing. At first, the piRNA binds to the targeted
sequence in DNA. Then the piRNA recruits silencing machinery components like Egg and its co-
factor WDE which together add repressive histone to the targeted DNA. Subsequently, a
heterochromatin protein 1 (HP1) is recruited in the site, which induce heterochromatin
formation which is transcriptionally inactive. Another way of gene silencing by piwi complex is
DNA methylation. It recruits DNA methyltransferase to methylate genic CpG sites, so the gene
cannot be transcribed. (12) The following figure shows the mechanism described above.
Figure 4 The gene silencing mechanism by piRNA (11)
The piRNA along with piwi proteins play pivotal role in spermatogenesis where they silence
mobile genetic elements called transposons. The silencing of transposons is carried out by post-
transcriptional transcript destruction. The piRNA binds to mature transposon transcript with
the help of Aub and Ago3. Then they undergo homology-dependent cleavage of transposon,
which helps the cell to maintain its genome. (13)
Reference
1) Watson, Patricia & Watson, Dennis. (2010). Alternative Splicing in Prostate and Breast Cancer. The Open
Cancer Journal. 3. 62-76. 10.2174/1874079001003010062.
2) Karijolich, J., & Yu, Y. T. (2010). Spliceosomal snRNA modifications and their function. RNA
biology, 7(2), 192–204. https://doi.org/10.4161/rna.7.2.11207
3) Brien Jacob, Hayder Heyam, Zayed Yara, Peng Chun (2018),Overview of MicroRNA Biogenesis,
Mechanisms of Actions, and Circulation,Frontiers in Endocrinology. 9. 405.
https://doi.org/10.3389/fendo.2018.00402
4) Liang, Junnan and Wen, Jingyuan and Huang, Zhao and Chen, Xiao-ping and Zhang, Bi-xiang and Chu,
Liang (2019). Small Nucleolar RNAs: Insight Into Their Function in Cancer. Frontiers in Oncology.9.587.
https://doi.org/10.3389/fonc.2019.00587
5) Tatello, L., Guo, CJ., Chen, LL. et al. Gene regulation by long non-coding RNAs and its biological
functions. Nat Rev Mol Cell Biol 22, 96–118 (2021). https://doi.org/10.1038/s41580-020-00315-9
6) T.H. Tran, M.A. Montano, in Translating MicroRNAs to the Clinic, 2017

7) Yu, Yi-Tao & Terns, Rebecca & Terns, Michael. (2004). Mechanisms and functions of RNA-guided RNA
modification. 10.1007/b105585)
8) Gerald Litwack Ph.D., in Human Biochemistry, 2018
9) Becares, M., Pascual-Iglesias, A., Nogales, A., Sola, I., Enjuanes, L., & Zuñiga, S. (2016). Mutagenesis of
Coronavirus nsp14 Reveals Its Potential Role in Modulation of the Innate Immune Response. Journal of
Virology, 90(11), 5399–5414. https://doi.org/10.1128/jvi.03259-15
10) Patrick Revy, Fabien Touzot, in Encyclopedia of Immunobiology, 2016
11) Czech, B., & Hannon, G. J. (2016b). One Loop to Rule Them All: The Ping-Pong Cycle and piRNA-
Guided Silencing. Trends in Biochemical Sciences, 41(4), 324–337.
https://doi.org/10.1016/j.tibs.2015.12.008
12) Liu, Y., Dou, M., Song, X. et al. The emerging role of the piRNA/piwi complex in cancer. Mol
Cancer 18, 123 (2019). https://doi.org/10.1186/s12943-019-1052-9
14) Macfarlane, L. A., & Murphy, P. R. (2010). MicroRNA: Biogenesis, Function and Role in Cancer. Current
genomics, 11(7), 537–561. https://doi.org/10.2174/138920210793175895
15) Yiwen Fang, Melissa J. Fullwood,Roles, Functions and Mechanisms of Long Non-coding RNAs in
Cancer, Genomics, Proteomics & Bioinformatics, Volume 14, Issue 1,2016,Pages 42-
54,https://doi.org/10.1016/j.gpb.2015.09.006

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Course: MCB303

Name: Noor-E-Khadiza Shama

Different types of RNA molecule and their functional

Small nuclear RNA (snRNA)

1. At first, the 5’-end of U1 snRNA recognize and binds to 5’ splice-site of pre-mRNA

Small nucleolar RNA (snoRNA)

Figure 3 The snoRNA guided methylation and pseudouridylation (7)

long non-coding RNA (lncRNA)

Piwi-interacting RNAs (piRNA)

Figure 4 The gene silencing mechanism by piRNA (11)

6) T.H. Tran, M.A. Montano, in Translating MicroRNAs to the Clinic, 2017

8) Gerald Litwack Ph.D., in Human Biochemistry, 2018

10) Patrick Revy, Fabien Touzot, in Encyclopedia of Immunobiology, 2016

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