Genetics Research

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April Lizeth D.

Reyes
BSE- Science 2B
Genetics

Types of Small RNA

Small regulatory RNAs play a crucial role when it comes to the gene’s expression
regulation, in the process of either binding to regulatory proteins or to target mRNAs
directly. Despite its name being small, sRNAs can actually be involved also in cell
differentiation, proliferation, migration, apoptosis, and metabolism. Given the sRNAs’
extraordinary capabilities, there are 3 main types of sRNAs; miRNAs, siRNAs, and
piRNAs.

- miRNAs or microRNAs regulate genes post- transcriptionally. In the 3’- UTR or


untranslated region of the mRNA is where it binds. Protein synthesis is
suppressed by disrupting mRNA and inhibiting translation. Recent studies have
shown that the stage of translation which is inhibited by miRNAs is dependent
upon the promoter used for transcribing the target mRNA.
https://pubmed.ncbi.nlm.nih.gov/19021530/
- The function of siRNAs, or small interfering RNAs, is to reduce the translation
of specific messenger RNAs in a sequential way particularly dependent on the
complementary binding of the target mRNA.
- Piwi- interacting RNA also possesses diverse capabilities; such as, embryonic
development, maintenance of germline DNA integrity, silencing of transposon
transcription, suppression of translation, formation of heterochromatin, and
epigenetic regulation of sex determination. Piwi proteins function on transposon
RNAs by cleaving them and interacting with RNA regulatory factors. PiRNAs
produced from transposons and pseudogenes can also be utilized by Piwi
proteins to modify mRNAs post-transcriptionally.

The new definition of Gene

When we are talking about inheritance of traits, the definition of gene would generally
be; An inherited factor that determines a characteristic. On the other hand, when we now
consider the complex nature of a gene; its structure, the process it undergoes, and how
it codes for genetic information, its definition would be specified and will be; A gene
consists of a set of DNA nucleotides. A gene is nowadays defined as a fragment of DNA
that codes for a functional protein or functional RNA that modifies phenotype, such as
tRNA, rRNA, or ribozymes. Whereas the technical or precise definition of gene is that; A
gene is a genomic sequence (DNA or RNA) directly encoding functional product
molecules, either RNA or protein.
Four major types of Introns

A human has an average of eight to nine introns. Both are being transcribed, but not
after Transcription. Introns are spliced, and exons stays. Prokaryotic cells were formerly
known to not have any introns, but it is now known that Archaea and some
Bacteriophages possesses it.

There are four major types of introns, and it is classified by the way they are spliced/
removed;

1. Group I Introns: They are located in Eubacteria genes, Bacteriophages, and


Eukaryotes. Introns under this type are known to be self- splicing.
2. Group II Introns: They all fold uniformly and have the ability to self-splice, its
mechanism though, is different from Group I. They are commonly found in
genes in mitochondria and chloroplasts, archaea, but they can also be found
in cyanobacteria and proteobacteria.
3. Nuclear pre- mRNA: Introns are located in the protein- encoding genes of
the nucleus of eukaryotes. The splicing mechanism is the same as the with
the group II, but the only thing is that Nuclear pre- mRNA is not self- splicing,
and requires specific proteins.
4. Transfer RNA Introns: These can be found in the genes of tRNA of both
prokaryotes and eukaryotes. Its splicing mechanism is heavily relied on
cutting enzymes.

Alternative processing pathways in RNA

In the understanding of a gene as a sequence of nucleotides, Alternative Processing


Pathways causes complications. A single pre-mRNA is processed in various ways to
generate multiple forms of mRNA, resulting in the creation of various proteins from the
same DNA sequence. Generally, there are two types of alternative processing;
alternative splicing, and multiple 3’ cleavage sites. But, both types produce different
mRNAs from a single pre- mRNA.

- Alternative splicing, where the same pre-mRNA can be spliced many times to
produce various mRNAs that translate into different amino acid sequences and
therefore different proteins
- Multiple 3’ cleavage sites, where it needs more than one potential site for
cleavage and polyadenylation to be present in the pre- mRNA.
RNA SPLICING; Exons Skipping and Introns Splicing

Exons are a portion of the RNA that code for proteins, specifically, amino acids. Exons
tend to be separated by incorporating introns, which are sections of DNA that do not
code for proteins. Upon Transcription, a pre- mRNA that contains both introns and exons
undergo a splicing process inside the nucleus; exons don’t literally go away, but stay in
the mature RNA and eventually code for amino acids, and introns are removed. When
genetic mutation happens, a couple of exons would be removed, resulting in errors and
would end up not having enough or no protein at all. Possible inherited diseases that
would turn out if such happens, are; Duchenne Muscular Dystrophy, and Developmental
Epileptic Encephalopathy, etc.

In the process of splicing introns, three sequences are necessary: 5' splice site, 3' splice
site, then branch point. Short consensus sequences can be found at the 5' and 3' splice
sites. Introns in pre-mRNA begin with GU and terminate with AG. A branch point is an
adenine nucleotide tract that contains up to 40 nucleotides from the 3' splice site.
Splicing is prevented by the deletion and mutation of the adenine nucleotide at the site.
Before the RNA can migrate into the cytoplasm, it must undergo RNA splicing in the
nucleus. Those that are not entirely spliced remain in the nucleus, up until the process of
splicing is complete. After that, exon- junction complex (EJC) deposits a rough amount of
20 nucleotides of each junction in the pre- mRNA. This protein is the one that indicates
the export of the mRNA to cytoplasm, coming from the nucleus. All these events, under
splicing, take place within the spliceosome.

RNA Interference

Eukaryotic cells use the potent and precise RNA interference mechanism to control both
the expression of their own genes and the invasion of foreign genes. The interference,
which can occur in a variety of ways, is started by the double-stranded RNA molecules.
Experimental biology could be altered by this endogenous mechanism for
sequence-specific gene silencing, which also has potential applications in other areas
such as agriculture, therapeutic intervention, and genomic research.

Double Stranded RNAs are made by the inverted repeats into an RNA molecule that
then base pairs with itself to form double- stranded RNA; by the simultaneous
transcription of two different RNA molecules that are complementary to one another. A
Dicer (enzyme) chops the Double Stranded RNA molecules to then create siRNAs and
miRNAs.
Many people believe that RNA Interference can protect against RNA viruses and
transposable elements that transit through RNA intermediates. The genome's immune
system is then referred to as RNAi. Furthermore, RNA interference is known to regulate
chromatin structure, translation, cell proliferation, and cell death. Furthermore, it can be
utilized to censor and inhibit gene expression.

RNA Editing and Mechanism

RNA editing is recognized to refer to the process and alteration of nucleotide sequences
in a wide range of organisms. RNA editing is indeed an important genetic regulating
mechanism that increases genetic flexibility by allowing the production of multiple protein
products from a particular gene.

- C- insertion in Mitochondrion Physarum


- U- insertion and deletion type of editing found in the mitochondrion of
kinetoplastid protozoa
- C-to-U substitution editing of the mammalian apoB mRNA

Processing and Function of microRNAs

Small RNA molecules known as microRNAs (miRNAs) degrade or prevent the


translation of mRNA when they link with complementary regions on the mRNA. Its length
is 22 nucleotides. A single-stranded RNA precursor that fragments into tiny hairpins is
the source of certain miRNAs. MiRNAs frequently only partially complement their target
mRNAs. Aside from the genes where the miRNAs were transcribed, it typically silences
other genes. Plant miRNAs have been found to have siRNA-like characteristics, such as
the capacity to cleave these sequences and exact complementarity with mRNA sections.
Every eukaryotic cell as well as viruses have been found to contain microRNAs. These
species' metabolism, growth, and development are all governed by miRNAs. In humans,
450 distinct microRNAs control more than one-third of our genes.

- It is derived from an RNA that has been transcribed from a certain gene.
- Is a cleavage of single-stranded RNA that results in the formation of short
double-stranded RNA hairpins.
- between 21 and 25 nucleotides
- Its functions include mRNA degradation, translation inhibition, and chromatin
modification.
- Genes other than those to which they were transcribed are its specific target.
References:

Pierce, B. A. (2014). Genetics: A conceptual approach. W.H. Freeman & Company.

Tamarin, R. H. (2004). Principles of Genetics. McGraw-Hill.

Zhang, C. (2009, December). Novel functions for small RNA molecules. Current opinion in
molecular therapeutics. Retrieved November 22, 2022, from
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3593927/#:~:text=It%20is%20generally%2
0agreed%20that,(piRNAs)%20%5B1%5D.

Suzuki, H., Aoki, Y., Kameyama, T., Saito, T., Masuda, S., Tanihata, J., Nagata, T.,
Mayeda, A., Takeda, S., & Tsukahara, T. (2016, October 13). Endogenous multiple exon
skipping and back-splicing at the DMD mutation hotspot. International journal of molecular
sciences. Retrieved November 22, 2022, from
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5085753/

U.S. National Library of Medicine. (2017, November 9). RNA interference (rnai). National
Center for Biotechnology Information. Retrieved November 22, 2022, from
https://www.ncbi.nlm.nih.gov/probe/docs/techrnai/#:~:text=RNA%20interference%20(RNAi
)%20or%20Post,expression%20of%20protein%2Dcoding%20genes.

Gerstein, M. B., Bruce, C., Rozowsky, J. S., Zheng, D., Du, J., Korbel, J. O.,
Emanuelsson, O., Zhang, Z. D., Weissman, S., & Snyder, M. (1970, January 1). What is a
gene, post-ENCODE? history and updated definition. Genome Research. Retrieved
November 22, 2022, from
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0definition&text=A%20gene%20is%20a%20genomic,genomic%20sequences%20coding
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