The transposable element-derived transcript of LIN28B has a placental origin and is not specific to tumors - article review
The transposable element-derived transcript of LIN28B (TEL-LIN28B) is a non-coding RNA that is derived from a transposable element (TE). TEs are mobile genetic elements that can insert themselves into the genome at random. TEL-LIN28B is thought to have originated in the placenta, and it is not specific to tumors.
Ancient ERVs are also TEs, but they are much older than TEL-LIN28B. Ancient ERVs are thought to have entered the genome of primates millions of years ago. While some ancient ERVs are now considered to be "junk DNA," others are known to play important roles in gene regulation.
The fact that TEL-LIN28B is derived from a TE and is not specific to tumors suggests that it may play a role in normal development. However, the exact function of TEL-LIN28B is still unknown.
Here is a table that summarizes the key differences between TEL-LIN28B and ancient ERVs:
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It is important to note that this is a complex topic, and there is still much that we do not know about TEL-LIN28B and ancient ERVs. However, the research that has been done so far suggests that these two types of TEs originate similarly in the past and may play important roles in development and disease.
Here is an illustration of primate placental evolution:
The illustration shows how the placenta has evolved in primates over time. The earliest primates, such as lemurs, have a simple, non-invasive placenta. This means that the placenta does not burrow into the uterine wall, but instead remains on the surface. This type of placenta is less efficient at transferring nutrients and oxygen to the fetus, and as a result, lemurs have relatively short gestation periods and give birth to small, underdeveloped young.
In more advanced primates, such as monkeys and apes, the placenta has become more invasive. This means that the placenta burrows into the uterine wall, creating a closer contact between the mother and fetus. This allows for more efficient transfer of nutrients and oxygen, and as a result, monkeys and apes have longer gestation periods and give birth to larger, more developed young.
In humans, the placenta has become even more invasive. The placenta not only burrows into the uterine wall, but it also sends out finger-like projections called villi. These villi increase the surface area of the placenta, which allows for even more efficient transfer of nutrients and oxygen to the fetus. As a result, human gestation periods are longer than any other primate, and human babies are born relatively large and developed.
The evolution of the placenta is a complex process that has been driven by a number of factors, including the need for more efficient nutrient and oxygen transfer to the fetus. The different types of placentas found in primates reflect the different dietary and ecological adaptations of these animals.
Transposable elements, also known as jumping genes (Junk DNA), are DNA sequences that can move from one location to another within a genome. They are a type of genetic mutation. Transposable elements can be harmful, beneficial, or neutral. They can cause diseases, but they can also play a role in evolution.
Neo-Darwinism is a modern synthesis of Charles Darwin's theory of evolution by natural selection and Mendelian genetics. It is the most widely accepted theory of evolution today. Neo-Darwinism states that evolution occurs through the accumulation of small, random changes in genes (mutations) over time. These mutations can be beneficial, harmful, or neutral. Beneficial mutations are more likely to be passed on to offspring, and over time, this can lead to the evolution of new species.
Transposable elements can work outside of neo-Darwinism in a few ways. First, they can cause mutations that are not caused by random chance. This is because transposable elements can insert themselves into genes, which can change the function of the gene. Second, transposable elements can increase the rate of evolution. This is because they can move genes from one organism to another, which can introduce new genetic variation into the population. Third, transposable elements can help to create new genes. This is because they can recombine different pieces of DNA, which can create new genes that are not present in either parent organism.
Overall, transposable elements are a powerful force of evolution. They can cause mutations, increase the rate of evolution, and create new genes. Transposable elements work outside of neo-Darwinism.
Article snippets:
June 2023
The transposable element-derived transcript of LIN28B has a placental origin and is not specific to tumors.
Transposable elements (TEs) are genetic elements that have evolved as crucial regulators of human development and cancer, functioning as both genes and regulatory elements.
When TEs become dysregulated in cancer cells, they can serve as alternate promoters to activate oncogenes, a process known as onco-exaptation.
This study aimed to explore the expression and epigenetic regulation of onco-exaptation events in early human developmental tissues
We discovered co-expression of some TEs and oncogenes in human embryonic stem cells and first trimester and term placental tissues.
Previous studies identified onco-exaptation events in various cancer types, including an AluJb SINE element–LIN28B interaction in lung cancer cells
This study further characterized the AluJb–LIN28B transcript and confirmed that its expression is restricted to the placenta
some TE–oncogene interactions are not cancer-specific but arise from the epigenetic reactivation of developmental TE-derived regulatory events.
our findings provide evidence that some TE–oncogene interactions are not limited to cancer and may originate from the epigenetic reactivation of TE-derived regulatory events that are involved in early development.
Initially, TEs were considered “junk DNA” with no functional role in gene expression or regulation.
TEs have significantly contributed to rapidly evolving gene regulatory networks during mammalian evolution (
Recruitment of TE sequences to function as bona fide genes and regulatory elements has been termed ‘exaptation’
Genes and regulatory elements that contain transposable element sequences can also be referred to as transposable element-derived and transposable element-regulated genes
TEs can function as regulators of nearby genes (in cis) and can also influence expression of distant genes (in trans).
There are now documented examples of TEs that function as protein-coding genes, long non-coding (lnc) RNAs, promoters, enhancers, insulators and boundary elements for topologically associated domain
trophoblasts (placental epithelial cells) and found that these elements were highly enriched for endogenous retroviral (ERV) sequences, and that retroviral recruitment was enriched in tissue types with lower levels of DNA methylation
Some of the first exaptation events were identified in the placenta
Perhaps the earliest example of TE-exaptation in the placenta was the discovery that envelope proteins (syncytins) function to enable the essential fusion of trophoblast cells during placentation
TEs have also been implicated in driving tissue specific expression of lncRNAs in the placenta.
The placenta is known to have lower levels of DNA methylation than adult somatic tissues, which has likely enabled by the unique methylation landscape of the placenta and may have facilitated the recruitment of somatically silenced TEs (
ERV-derived enhancer elements are mediated by GATA 2/3 and MSX2 in trophoblast cells and have a role in both repression and activation of trophoblast gene regulatory networks
Altogether, this suggests that lower levels of DNA methylation at some TE loci may have facilitated the recruitment of normally silenced TEs, thus enabling the evolution and diversification of new regulatory networks in the placenta.
Furthermore, many TEs are dynamically regulated throughout early human development and functional TEs tend to be highly cell and stage specifically expressed
the placenta possesses unique functional properties that are exclusive to placentation and are not seen in any other healthy somatic tissues
The human placenta shares striking similarities with cancer cells
During the first trimester of pregnancy, the trophoblast cells of the placenta invade into the uterine wall to seek out a blood supply for the developing fetus. Similarly, cancer cells also invade into the surrounding tissue to seek out a bloody supply and sustain growth
both tissues exhibit manipulation of the host immune system to prevent recognition and immunological rejection
there is evidence to suggest that species that have evolved to allow extensive invasion of the placenta show a higher incidence of epithelial cancers
dedifferentiation of tumour cells may play a key role in facilitating this, through enabling increased phenotypic plasticity.
the fundamental regulators of pluripotency are all potent oncogenes, suggesting that cancers can repurpose developmental genes to drive malignancy
We, therefore, hypothesised that some onco-exaptation events occur because of epigenetic reactivation of TE–gene regulatory relationships that exist in early human developmental tissues and that these may enable cancers to recapitulate some of the properties of early developmental tissues
this study provides novel insights into the potential role of TEs in regulating gene expression during development and disease
Our findings demonstrate that some TE–oncogene interactions may not be cancer-specific but rather arise from the epigenetic reactivation of TE-derived regulatory events that are involved in early development
In addition, our findings suggest that the involvement of TEs in gene regulation during development may be more widespread than previously thought, highlighting the need for further studies to better understand the potential role of TEs in normal physiology.
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