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Let-7 microRNA family
The Let-7 microRNA precursor gives rise to let-7, a microRNA (miRNA) involved in control of stem-cell division and differentiation. let-7, short for "lethal-7", was discovered along with the miRNA lin-4 in a study of developmental timing in C. elegans, making these miRNAs the first ever discovered. let-7 was later identified in humans as the first human miRNA, and is highly conserved across many species. Dysregulation of let-7 contributes to cancer development in humans by preventing differentiation of cells, leaving them stuck in a stem-cell like state. let-7 is therefore classified as a tumor suppressor.
The let-7 microRNA family refers to the many slight variations of let-7 that exist both within a single organism and across species. In humans, for example, there are ten unique let-7 family member sequences: let-7a through g, let-7i, mir-98, and mir-202.
In humans, mature let-7 acts via RNA-induced silencing by complexing with RISC and binding to target mRNA, preventing translation into protein. Known targets of let-7 include proteins related to the cell cycle and proliferation, such as MYC, RAS, cyclin D, HMGA2, and CDC25A. Knockdown of these proteins by let-7 prevents proliferation and induces differentiation of cells. Important inhibitors of let-7 include LIN28, which binds to let-7 directly, and the proto-oncogene MYC, which suppresses expression.
In human genome, the cluster let-7a-1/let-7f-1/let-7d is inside the region B at 9q22.3, with the defining marker D9S280-D9S1809. One minimal LOH (loss of heterozygosity) region, between loci D11S1345-D11S1316, contains the cluster miR-125b1/let-7a-2/miR-100. The cluster miR-99a/let-7c/miR-125b-2 is in a 21p11.1 region of HD (homozygous deletions). The cluster let-7g/miR-135-1 is in region 3 at 3p21.1-p21.2.
The lethal-7 (let-7) gene was first discovered in the nematode C. elegans as a key developmental regulator and became one of the first two known microRNAs (the other one is lin-4). Soon, let-7 was found in the fruit fly (Drosophila), and identified as the first known human miRNA by a BLAST (basic local alignment search tool) research. The mature form of let-7 family members is highly conserved across species.
In C. elegans, the let-7 family consists of genes encoding nine miRNAs sharing the same seed sequence. Among them, let-7, mir-84, mir-48 and mir-241 are involved in the C. elegans heterochronic pathway, sequentially controlling developmental timing of larva transitions. Most animals with loss-of-function let-7 mutation burst through their vulvas and die, and therefore the mutant is lethal (let). The mutants of other let-7 family members have a radio-resistant phenotype in vulval cells, which may be related to their ability to repress RAS.
There is only one single let-7 gene in the Drosophila genome, which has the identical mature sequence to the one in C. elegans. The role of let-7 has been demonstrated in regulating the timing of neuromuscular junction formation in the abdomen and cell-cycle in the wing. Furthermore, the expression of pri-, pre- and mature let-7 have the same rhythmic pattern with the hormone pulse before each cuticular molt in Drosophila.
The let-7 family has a lot more members in vertebrates than in C. elegans and Drosophila. The sequences, expression timing, as well as genomic clustering of these miRNAs members are all conserved across species. The direct role of let-7 family in vertebrate development has not been clearly shown as in less complex organisms, yet the expression pattern of let-7 family is indeed temporally regulated during developmental processes. Functionally, let-7 has been shown in early vertebrates to control the differentiation of mesoderm and ectoderm. Given that the expression levels of let-7 members are significantly low in human cancers and cancer stem cells, the major function of let-7 genes may be to promote terminal differentiation in development and tumor suppression.
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Let-7 microRNA family AI simulator
(@Let-7 microRNA family_simulator)
Let-7 microRNA family
The Let-7 microRNA precursor gives rise to let-7, a microRNA (miRNA) involved in control of stem-cell division and differentiation. let-7, short for "lethal-7", was discovered along with the miRNA lin-4 in a study of developmental timing in C. elegans, making these miRNAs the first ever discovered. let-7 was later identified in humans as the first human miRNA, and is highly conserved across many species. Dysregulation of let-7 contributes to cancer development in humans by preventing differentiation of cells, leaving them stuck in a stem-cell like state. let-7 is therefore classified as a tumor suppressor.
The let-7 microRNA family refers to the many slight variations of let-7 that exist both within a single organism and across species. In humans, for example, there are ten unique let-7 family member sequences: let-7a through g, let-7i, mir-98, and mir-202.
In humans, mature let-7 acts via RNA-induced silencing by complexing with RISC and binding to target mRNA, preventing translation into protein. Known targets of let-7 include proteins related to the cell cycle and proliferation, such as MYC, RAS, cyclin D, HMGA2, and CDC25A. Knockdown of these proteins by let-7 prevents proliferation and induces differentiation of cells. Important inhibitors of let-7 include LIN28, which binds to let-7 directly, and the proto-oncogene MYC, which suppresses expression.
In human genome, the cluster let-7a-1/let-7f-1/let-7d is inside the region B at 9q22.3, with the defining marker D9S280-D9S1809. One minimal LOH (loss of heterozygosity) region, between loci D11S1345-D11S1316, contains the cluster miR-125b1/let-7a-2/miR-100. The cluster miR-99a/let-7c/miR-125b-2 is in a 21p11.1 region of HD (homozygous deletions). The cluster let-7g/miR-135-1 is in region 3 at 3p21.1-p21.2.
The lethal-7 (let-7) gene was first discovered in the nematode C. elegans as a key developmental regulator and became one of the first two known microRNAs (the other one is lin-4). Soon, let-7 was found in the fruit fly (Drosophila), and identified as the first known human miRNA by a BLAST (basic local alignment search tool) research. The mature form of let-7 family members is highly conserved across species.
In C. elegans, the let-7 family consists of genes encoding nine miRNAs sharing the same seed sequence. Among them, let-7, mir-84, mir-48 and mir-241 are involved in the C. elegans heterochronic pathway, sequentially controlling developmental timing of larva transitions. Most animals with loss-of-function let-7 mutation burst through their vulvas and die, and therefore the mutant is lethal (let). The mutants of other let-7 family members have a radio-resistant phenotype in vulval cells, which may be related to their ability to repress RAS.
There is only one single let-7 gene in the Drosophila genome, which has the identical mature sequence to the one in C. elegans. The role of let-7 has been demonstrated in regulating the timing of neuromuscular junction formation in the abdomen and cell-cycle in the wing. Furthermore, the expression of pri-, pre- and mature let-7 have the same rhythmic pattern with the hormone pulse before each cuticular molt in Drosophila.
The let-7 family has a lot more members in vertebrates than in C. elegans and Drosophila. The sequences, expression timing, as well as genomic clustering of these miRNAs members are all conserved across species. The direct role of let-7 family in vertebrate development has not been clearly shown as in less complex organisms, yet the expression pattern of let-7 family is indeed temporally regulated during developmental processes. Functionally, let-7 has been shown in early vertebrates to control the differentiation of mesoderm and ectoderm. Given that the expression levels of let-7 members are significantly low in human cancers and cancer stem cells, the major function of let-7 genes may be to promote terminal differentiation in development and tumor suppression.