BB1801 Report: Pseudogenes - Types, Functions, and Regulatory Roles

This report provides a detailed overview of pseudogenes, which are non-functional segments of DNA that share homology with functional genes. It explores the biogenesis and classification of pseudogenes, including processed, unprocessed, duplicated, unitary, and pseudo-pseudogenes. The report highlights the various functions of pseudogenes, such as their regulatory roles in gene expression, their involvement in genetic diversity, and their influence on the activity of other genes. It provides examples like the Ir75a pseudogene in Drosophila and the BRAF pseudogene in cancer. The report also discusses the role of pseudogenes like PTENP1 in tumor suppression, emphasizing their significance in understanding genomic DNA changes and their implications in biochemical pathways, gene regulation, and potential therapeutic targets.

PSUEDOGENE
Pseudogenes are the segment of DNA molecule that
are similar to functional gene but has lost the ability to
code for protein. They are defined as the gene that has
been mutated into inactive form and often lack introns
and other required DNA sequence. The discovery of
pseudogene took place in the year 1977 by Jacq and
co-workers from 5SrRNA in Xenopus laevis, The
truncated gene showed homology with the active gene
but was unable to produce any protein. The biogenesis
of pseudogene occurred by duplication of parental DNA
or process of reverse transcriptase. Currently, there are
total of 20,000 pseudogene identified which are
comparable with 27000 gene of human being. It is
reported in the recent studies, they tends to act as the
origin of genetic diversity and function in production of
antibodies and antigen variation. They are also known to
control the regulation of specific gene function for
exampleABCC6 mRNA (Milligan and Lipovich 2015).
Psuedogene classification and types
Pseudogene are classified based on the mechanism of
formation into various categories:
• PROCESSED PSEUDOGENE- They originate by retro-
transposition, where the CDNA undergo replication by the
enzyme known as reverse transcriptase.
• UN-PROCESSED PSEUDOGENE- They usually contains
introns and situated next to parent DNA. They are raise by
the mutation where the extra copy of gene which are
functional undergo duplication and retain introns. Their
expressions are crippled by stop codon.
Psuedogene activity and function
Pseudogene are known to have several
function which has been observed in course of
evolution. These genes are known to influence
the function of gene by their regulatory action
(Grandér and Johnsson 2015). It is also known
to control the overexpression of the
transcription factors that are pluripotent. It is
evident from the research that antisense
pseudogene associate with the genic transcript
and regulate the gene expression. For example
oct4 pseudogene are known to inhibit the cell
differentiation (Lettnin et al. 2019).
Reference
Types of pseudogene
• The classification of pseudogene are divided it into two different types:
• DUPLICATED PSEUDOGENE- Originated through duplication of
unprocessed DNA. They keep their exon and intron structure intact.
• UNITARY PSEUDOGENE- They are also unprocessed form which have
active ortholog in different species. In this the single copy of the parent
gene undergo changes to become non-functional.
• PSEUDO- PSEUDOGENE is other type of pseudogene which is
identified by the emergence of stop codon in the Mrna sequence. It
prevent the translation of the normal protein of the original gene. It is
formed with course of evolution where there is insertion of stop codon in
normal functioning gene and through natural selection the gene gets
selected in the next generations.
•
Lastly, from the above discussion, it can be said that,
pseudogene, though not having nay function in production of
protein, it is very crucial for expression of gene which is known to
have vital role in functioning of body. Psuedogene are important
as they give fundamental record of process of change of
genomic DNA with course of evolution. Thus, it is important for
studying the pseudogene as it will help to know about the
essential biochemical pathway of gene and regulation. The study
will reveal about mechanism of gene involved in cancer and new
treatment option.
Example of function of psuedogene function
• In drosophila, the Ir75a pseudogene are known to create the functional
receptor which translate the pre-mature termination codon. Thus helps
in expression of ionotropic glutamate receptor.
• Some siRNA emerged from pseudogene which has major role in
regulation of protein coding transcript.
• PiRNA also derived from the pseudogene and function to limit the
damage of transposal element.
• It is evident from recent studies that there are many transcript of
pseudogene which act as micor-RNA. For example, pseudogene
indulge in cancer is BRAF. It is the type of proto-oncogene, which on
mutation result in various type of cancer. The level of BRAF is
maintained by the action of miRNA ((Karreth et al. 2015 ).
• Pseudogene function is also related to tumour suppressor gene.
PTENP1 is the type of pseudogene which act as TSG and originate by
missense mutation. It eliminates the initiation codon methionine and
prevents the generation of normal PTEN gene. Thus, it also contributes
to emergence of various type of cancer tumour (Lister et al. 2017).
Grandér, D. and Johnsson, P., 2015. Pseudogene-expressed RNAs: emerging roles in gene
regulation and disease. In Long Non-coding RNAs in Human Disease (pp. 111-126). Springer,
Cham.
Grandi, N., Cadeddu, M., Blomberg, J. and Tramontano, E., 2016. Contribution of type W
human endogenous retroviruses to the human genome: characterization of HERV-W proviral
insertions and processed pseudogenes. Retrovirology, 13(1), p.67.
Karreth, F.A., Reschke, M., Ruocco, A., Ng, C., Chapuy, B., Léopold, V., Sjoberg, M., Keane,
T.M., Verma, A., Ala, U. and Tay, Y., 2015. The BRAF pseudogene functions as a competitive
endogenous RNA and induces lymphoma in vivo. Cell, 161(2), pp.319-332.
Lettnin, A.P., Wagner, E.F., Carrett-Dias, M., dos Santos Machado, K., Werhli, A., Cañedo,
A.D., Trindade, G.S. and de Souza Votto, A.P., 2019. Silencing the OCT4-PG1 pseudogene
reduces OCT-4 protein levels and changes characteristics of the multidrug resistance
phenotype in chronic myeloid leukemia. Molecular biology reports, 46(2), pp.1873-1884.
Lister, N., Shevchenko, G., Walshe, J.L., Groen, J., Johnsson, P., Vidarsdóttir, L., Grander, D.,
Ataide, S.F. and Morris, K.V., 2017. The molecular dynamics of long noncoding RNA control of
transcription in PTEN and its pseudogene. Proceedings of the National Academy of
Sciences, 114(37), pp.9942-9947.
Milligan, M.J. and Lipovich, L., 2015. Pseudogene-derived lncRNAs: emerging regulators of
gene expression. Frontiers in genetics, 5, p.476.
Conclusion
Introduction
Pseudogene types