Scientists at the U.S. Whitehead Institute have identified a conserved long intervening noncoding RNA (lincRNA) that plays a key role in brain development in zebrafish embryos. They also confirmed that the human lincRNA version can replace the zebrafish lincRNA version, suggesting that the function of these non-coding RNAs is also maintained in humans. On December 23, 2011, these findings were published in the journal Cell.
Prior to this, the research on lincRNAs was mainly carried out on cell lines rather than at the organism level, which ruled out how lincRNA affects growth and development studies.
David Bartel, a member of the Baldwin Institute, a researcher at the Howard Hughes Medical Institute and a professor of biology at the Massachusetts Institute of Technology, said: "These studies show that zebrafish, a genetic often used to study animal development The model animal - able to systematically reveal the function of lincRNA as a research tool. This is another case in which the findings in zebrafish may also apply to humans."
Human cells transcribe only a small amount of RNA as a template for expressing the protein. Other RNAs are called non-coding RNAs (ncRNAs) and they are located between the genes encoding the proteins. ncRNAs with a length of no less than 200 bases are called lincRNAs.
Although they are abundant in cells, lincRNA has long been considered as a “dark matter†in all transcribed RNA because people know very little about their function or mechanism of action. One limitation of studying such RNA is that they are between different species. There is a lower sequence similarity. Unlike genes that often conserve proteins that are conserved between species, the lincRNA gene usually has very few conserved DNA sequences between species. This lack of conservation makes it difficult to identify related lincRNAs among closely related species, but not among species with relatively close genetic relationships. For example, Bartel laboratory scientists Igor Ulitsky and Alena Shkumatava identified more than 500 lincRNAs in zebrafish, but only 20 were found to be homologous in humans and mice.
Ulitsky and Shkumatava tested two of these 29 lincRNAs in this study. The method used was to inhibit both lincRNAs in zebrafish embryos. Inhibition of these two lincRNAs has a significant effect on the brain development of zebrafish. The reduction of one of these two lincRNAs, their cyrano-derived lincRNA, causes the zebrafish to have enlarged nose, small heads and eyes, short and curly tails, and the zebrafish lacking the lincRNA they call megamind has an unusually shaped head. And the enlarged ventricles.
To test whether the human homologs of the two crynotypes, cyrano and megamind, are functionally equivalent, Shkumatava was injected with a human lincRNA version into the gene-suppressed zebrafish. Remarkably, human lincRNAs rescued zebrafish and restored brain development and brain size, suggesting that human lincRNAs may have the same role in embryonic development as their zebrafish homologues.
Michael Bender, the National Institute of Integrated Medical Sciences at the National Institutes of Health who oversees funding for RNA processing and functionality, said: "This study represents a major advance because it provides research on lincRNA - a type that people know little about. But there are also a large number of existing molecules -- the study found that human lincRNAs appear to be very similar to their zebrafish counterparts in their role in embryonic development, which means that this method will be used to understand the role of lincRNA in mammals. Role provides very valuable inspiration."
Baekdusan research member Hazel Sive worked with Bartel and other laboratory members to use zebrafish to study brain development and gene mutations associated with autism. Sive said, "The zebrafish is an excellent and easy-to-use system for discovering the working mechanism of genes."
Ulitsky said, “We humans share this small and ancient and exotic gene with zebrafish, and their function is preserved in zebrafish and humans. We can destroy them in zebrafish and then replace them with human genes, at least in On the lincRNA we studied, human genes worked to restore the correct development of the zebrafish," Shkumatava said. "Because of this functional conservation of lincRNA between zebrafish and humans, we are using the zebrafish as a new type of spine. Animal research tools can be used to reveal the function of other lincRNAs."
Scientists from the Whitehead Institute for Biomedical Research have recently identified conserved intercalating long-chain noncoding RNAs (lincRNAs) that play a key role in brain development in zebrafish. And confirmed that these RNAs from humans have similar functions as lincRNAs in zebrafish. The study was found on December 23 in the Cell magazine.
So far, the study of lincRNAs has mainly been carried out at the cell line rather than at the organism level, which has prevented researchers from gaining insight into how lincRNAs affect growth and development.
"These studies show that zebrafish, a model animal commonly used to study animal developmental genetics, can also be used as a research tool to systematically reveal the function of lincRNAs," said Whitehead Institute of Biomedical Research, Howard 's 8226; Researcher Hughes Medical Institute and Professor MIT Department of Biology Professor David Bartel said: "This is another example of deep understanding of human-related mechanisms through the analysis of the phenomenon in zebrafish. Previously this method was used in a large number of Protein-coding genes."
According to a 2007 study by the Encyclopedia of DNA Elements (ENCODE) Association, only a few transcriptionally generated RNAs in human cells serve as a template for protein synthesis. The rest of the RNA is called non-coding RNAs (ncRNAs) and they are located between the genes encoding the protein, and ncRNAs longer than 200 bp are called lincRNAs.
Although there are a large number of lincRNAs in cells, they have long been regarded as "dark matter" in transcribed RNAs, and little is known about their functions and mechanisms. An important limitation of studying the existence of such RNAs is that they show lower sequence similarity between species. Unlike protein-coding genes, which often show high conservation among species, lincRNA genes usually have only a few conserved DNA sequences between species. This lack of conservation makes it difficult to identify related lincRNAs between closely related species, not to mention distantly related species. For example, Bartel laboratory scientists Igor Ulitsky and Alena Shkumatava identified more than 500 lincRNAs in zebrafish, but only 29 homologs were found in humans and mice.
In this new Cell article, Ulitsky and Shkumatava used antisense technology to perform functional assays on two of the 29 types of lincRNAs in zebrafish embryos. The results suggest that inhibition of these two lincRNAs can significantly affect the brain development of zebrafish. When the expression of one of the lincRNAs, called cyrano, declines, it can cause zebrafish to form large noses, small heads and small eyes, and short and curly tails. When a zebrafish misses a lincRNA called megamind, it can cause it to form abnormally shaped heads and enlarged ventricles.
To test if homologs of cyrano and megamind lincRNAs in human cells have the same function. Shkumatava injected human homologous lincRNAs into knockout zebrafish. Amazingly, these human lincRNAs rescued zebrafish, restoring normal brain development and brain size, suggesting that human lincRNAs may play the same role in embryonic development as their zebrafish homologues. .
"This study is of great significance because it provides us with a way to study this type of abundant and poorly understood lincRNAs," said National Institute of General Medical Sciences under the National Institutes of Health. Project research funding director Michael Bender said: "This study found that human lincRNAs appear to exhibit similar functions in their embryonic development as their zebrafish homologues, suggesting that this method is of great value to motivate researchers to gain insight into lincRNAs. Role in mammals."
Hazel Sive, currently a member of the Whitehead Institute of Biomedical Research, has collaborated with Bartel Laboratories to use zebrafish to study brain development and genetic defects associated with autism. Sive said: "The zebrafish is an excellent and easy-to-operate system suitable for studying the mechanism of action of genes."
“We humans and zebrafish share this ancient and unique genetic subpopulation, and their function is preserved in humans and zebrafish,†Ulitsky said. “We can replace damaged zebrafish by using human homologs. The way of lincRNAs to understand which human lincRNAs have regulatory developmental roles."
"Because of the functional conservation of lincRNAs in zebrafish and humans, we can use zebrafish as a new vertebrate research tool to reveal the function of other lincRNAs," Shkumatava said.
Prior to this, the research on lincRNAs was mainly carried out on cell lines rather than at the organism level, which ruled out how lincRNA affects growth and development studies.
David Bartel, a member of the Baldwin Institute, a researcher at the Howard Hughes Medical Institute and a professor of biology at the Massachusetts Institute of Technology, said: "These studies show that zebrafish, a genetic often used to study animal development The model animal - able to systematically reveal the function of lincRNA as a research tool. This is another case in which the findings in zebrafish may also apply to humans."
Human cells transcribe only a small amount of RNA as a template for expressing the protein. Other RNAs are called non-coding RNAs (ncRNAs) and they are located between the genes encoding the proteins. ncRNAs with a length of no less than 200 bases are called lincRNAs.
Although they are abundant in cells, lincRNA has long been considered as a “dark matter†in all transcribed RNA because people know very little about their function or mechanism of action. One limitation of studying such RNA is that they are between different species. There is a lower sequence similarity. Unlike genes that often conserve proteins that are conserved between species, the lincRNA gene usually has very few conserved DNA sequences between species. This lack of conservation makes it difficult to identify related lincRNAs among closely related species, but not among species with relatively close genetic relationships. For example, Bartel laboratory scientists Igor Ulitsky and Alena Shkumatava identified more than 500 lincRNAs in zebrafish, but only 20 were found to be homologous in humans and mice.
Ulitsky and Shkumatava tested two of these 29 lincRNAs in this study. The method used was to inhibit both lincRNAs in zebrafish embryos. Inhibition of these two lincRNAs has a significant effect on the brain development of zebrafish. The reduction of one of these two lincRNAs, their cyrano-derived lincRNA, causes the zebrafish to have enlarged nose, small heads and eyes, short and curly tails, and the zebrafish lacking the lincRNA they call megamind has an unusually shaped head. And the enlarged ventricles.
To test whether the human homologs of the two crynotypes, cyrano and megamind, are functionally equivalent, Shkumatava was injected with a human lincRNA version into the gene-suppressed zebrafish. Remarkably, human lincRNAs rescued zebrafish and restored brain development and brain size, suggesting that human lincRNAs may have the same role in embryonic development as their zebrafish homologues.
Michael Bender, the National Institute of Integrated Medical Sciences at the National Institutes of Health who oversees funding for RNA processing and functionality, said: "This study represents a major advance because it provides research on lincRNA - a type that people know little about. But there are also a large number of existing molecules -- the study found that human lincRNAs appear to be very similar to their zebrafish counterparts in their role in embryonic development, which means that this method will be used to understand the role of lincRNA in mammals. Role provides very valuable inspiration."
Baekdusan research member Hazel Sive worked with Bartel and other laboratory members to use zebrafish to study brain development and gene mutations associated with autism. Sive said, "The zebrafish is an excellent and easy-to-use system for discovering the working mechanism of genes."
Ulitsky said, “We humans share this small and ancient and exotic gene with zebrafish, and their function is preserved in zebrafish and humans. We can destroy them in zebrafish and then replace them with human genes, at least in On the lincRNA we studied, human genes worked to restore the correct development of the zebrafish," Shkumatava said. "Because of this functional conservation of lincRNA between zebrafish and humans, we are using the zebrafish as a new type of spine. Animal research tools can be used to reveal the function of other lincRNAs."
Scientists from the Whitehead Institute for Biomedical Research have recently identified conserved intercalating long-chain noncoding RNAs (lincRNAs) that play a key role in brain development in zebrafish. And confirmed that these RNAs from humans have similar functions as lincRNAs in zebrafish. The study was found on December 23 in the Cell magazine.
So far, the study of lincRNAs has mainly been carried out at the cell line rather than at the organism level, which has prevented researchers from gaining insight into how lincRNAs affect growth and development.
"These studies show that zebrafish, a model animal commonly used to study animal developmental genetics, can also be used as a research tool to systematically reveal the function of lincRNAs," said Whitehead Institute of Biomedical Research, Howard 's 8226; Researcher Hughes Medical Institute and Professor MIT Department of Biology Professor David Bartel said: "This is another example of deep understanding of human-related mechanisms through the analysis of the phenomenon in zebrafish. Previously this method was used in a large number of Protein-coding genes."
According to a 2007 study by the Encyclopedia of DNA Elements (ENCODE) Association, only a few transcriptionally generated RNAs in human cells serve as a template for protein synthesis. The rest of the RNA is called non-coding RNAs (ncRNAs) and they are located between the genes encoding the protein, and ncRNAs longer than 200 bp are called lincRNAs.
Although there are a large number of lincRNAs in cells, they have long been regarded as "dark matter" in transcribed RNAs, and little is known about their functions and mechanisms. An important limitation of studying the existence of such RNAs is that they show lower sequence similarity between species. Unlike protein-coding genes, which often show high conservation among species, lincRNA genes usually have only a few conserved DNA sequences between species. This lack of conservation makes it difficult to identify related lincRNAs between closely related species, not to mention distantly related species. For example, Bartel laboratory scientists Igor Ulitsky and Alena Shkumatava identified more than 500 lincRNAs in zebrafish, but only 29 homologs were found in humans and mice.
In this new Cell article, Ulitsky and Shkumatava used antisense technology to perform functional assays on two of the 29 types of lincRNAs in zebrafish embryos. The results suggest that inhibition of these two lincRNAs can significantly affect the brain development of zebrafish. When the expression of one of the lincRNAs, called cyrano, declines, it can cause zebrafish to form large noses, small heads and small eyes, and short and curly tails. When a zebrafish misses a lincRNA called megamind, it can cause it to form abnormally shaped heads and enlarged ventricles.
To test if homologs of cyrano and megamind lincRNAs in human cells have the same function. Shkumatava injected human homologous lincRNAs into knockout zebrafish. Amazingly, these human lincRNAs rescued zebrafish, restoring normal brain development and brain size, suggesting that human lincRNAs may play the same role in embryonic development as their zebrafish homologues. .
"This study is of great significance because it provides us with a way to study this type of abundant and poorly understood lincRNAs," said National Institute of General Medical Sciences under the National Institutes of Health. Project research funding director Michael Bender said: "This study found that human lincRNAs appear to exhibit similar functions in their embryonic development as their zebrafish homologues, suggesting that this method is of great value to motivate researchers to gain insight into lincRNAs. Role in mammals."
Hazel Sive, currently a member of the Whitehead Institute of Biomedical Research, has collaborated with Bartel Laboratories to use zebrafish to study brain development and genetic defects associated with autism. Sive said: "The zebrafish is an excellent and easy-to-operate system suitable for studying the mechanism of action of genes."
“We humans and zebrafish share this ancient and unique genetic subpopulation, and their function is preserved in humans and zebrafish,†Ulitsky said. “We can replace damaged zebrafish by using human homologs. The way of lincRNAs to understand which human lincRNAs have regulatory developmental roles."
"Because of the functional conservation of lincRNAs in zebrafish and humans, we can use zebrafish as a new vertebrate research tool to reveal the function of other lincRNAs," Shkumatava said.
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