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Related Concept Videos

MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...
Mismatch Repair01:20

Mismatch Repair

Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
Mutations in Microorganisms01:18

Mutations in Microorganisms

Mutations are heritable changes in an organism’s genome involving alterations in the base sequence of DNA or RNA. These changes can influence cellular processes and phenotypic traits, potentially transforming the unaltered wild type into a mutant form. Such changes, termed forward mutations, are pivotal in shaping the genetic diversity of organisms.RNA viruses exhibit the highest mutation rates due to the absence of robust proofreading mechanisms during genome replication. In contrast,...

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Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library
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Published on: April 6, 2012

Mutagen-specific mutation signature determines global microRNA binding.

Eyal Greenberg1, Gideon Rechavi, Ninette Amariglio

  • 1Ella Institute of Melanoma, Sheba Medical Center, Ramat-Gan, Israel.

Plos One
|November 19, 2011
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Summary

UV radiation causes melanoma by disrupting micro-RNA (miRNA) gene regulation. Mutations reduce miRNA binding, promoting cancer development, especially in light-skinned populations with less 3'UTR GC content.

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Identifying Targets of Human microRNAs with the LightSwitch Luciferase Assay System using 3'UTR-reporter Constructs and a microRNA Mimic in Adherent Cells
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Identifying Targets of Human microRNAs with the LightSwitch Luciferase Assay System using 3'UTR-reporter Constructs and a microRNA Mimic in Adherent Cells
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MicroRNA Amplification and Recognition through Locked-nucleic-acid In situ Hybridization as a Novel Detection and Quantification Method

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Area of Science:

  • Genetics
  • Molecular Biology
  • Cancer Research

Background:

  • Micro-RNAs (miRNAs) are key post-transcriptional gene regulators.
  • Dysregulation of miRNA activity is implicated in cancer development.
  • UV radiation is a primary cause of melanoma.

Purpose of the Study:

  • To investigate the impact of UV-induced mutations on miRNA binding in melanoma.
  • To explore the role of miRNA dysregulation in UV-driven carcinogenesis.
  • To examine population-based differences in 3'UTR sequence affecting miRNA regulation.

Main Methods:

  • Whole genome sequencing of melanoma tumors.
  • Computational prediction using three algorithms to assess miRNA-3'UTR binding.
  • Analysis of mutation patterns in UV-induced versus non-UV-induced cancers.
  • Comparison of 3'UTR SNP GC content across different skin pigmentation populations.

Main Results:

  • Melanoma somatic mutations, particularly C-to-T, globally reduce miRNA binding to 3'UTRs.
  • Seed regions in miRNAs show Guanine enrichment, further impairing binding to mutated 3'UTRs.
  • Mutation patterns in lung cancer and leukemia do not predict similar miRNA binding disruption.
  • Dark-skinned populations exhibit higher 3'UTR SNP GC content than light-skinned populations.

Conclusions:

  • UV-induced disruption of miRNA-mediated gene regulation is a significant factor in melanoma development.
  • Evolutionary pressure may favor higher GC content in 3'UTRs for UV protection in certain populations.
  • Understanding these mechanisms can inform cancer prevention and treatment strategies.