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Related Concept Videos

MicroRNAs01:22

MicroRNAs

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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...
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Nucleic Acid Structure01:25

Nucleic Acid Structure

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The pentose sugar in DNA is deoxyribose, while in RNA the pentose sugar is ribose. The difference between the sugars is the presence of the hydroxyl group on the ribose's second carbon and a hydrogen on the deoxyribose's second carbon. The phosphate residue attaches to the hydroxyl group of the 5′ carbon of one sugar and the hydroxyl group of the 3′ carbon of the sugar of the next nucleotide, which forms  a 5′ to 3′ phosphodiester linkage.
DNA Structure
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RNA Interference01:23

RNA Interference

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RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
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piRNA - Piwi-interacting RNAs02:57

piRNA - Piwi-interacting RNAs

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PIWI-interacting RNAs, or piRNAs, are the most abundant short non-coding RNAs. More than 20,000 genes have been found in humans that code for piRNAs while only 2000 genes have been found for miRNAs. piRNAs can act at the transcriptional and post-transcriptional levels and have a vital role in silencing transposable elements present in germ cells. They are also involved in epigenetic silencing and activation. Previously, they were thought to function only in germ cells but new evidence suggests...
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siRNA - Small Interfering RNAs02:30

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Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
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Nonsense-mediated mRNA Decay02:27

Nonsense-mediated mRNA Decay

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The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
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A Reporter Assay to Analyze Intronic microRNA Maturation in Mammalian Cells
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Dynamic Protein-RNA recognition in primary MicroRNA processing.

Victor M Ruiz-Arroyo1, Yunsun Nam1

  • 1Department of Biochemistry, Department of Biophysics, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Current Opinion in Structural Biology
|September 6, 2022
PubMed
Summary
This summary is machine-generated.

MicroRNAs regulate gene expression through precise processing. Structural features, not sequence, guide recognition by the Microprocessor complex (Drosha-DGCR8), enabling diverse RNA binding.

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Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • MicroRNAs (miRNAs) are key regulators of gene expression, controlling a significant portion of the proteome in multicellular organisms.
  • Efficient and accurate biogenesis of functional small RNAs, including miRNAs, necessitates precise processing steps.
  • The Microprocessor complex, comprising Drosha and DGCR8, initiates miRNA biogenesis in animals, a critical step for selecting primary miRNAs.

Purpose of the Study:

  • To elucidate the structural basis of substrate recognition by the Microprocessor complex.
  • To understand the dynamic mechanisms of protein-RNA complex assembly and disassembly in miRNA maturation.
  • To compare the recognition strategies of Microprocessor and Dicer homologs.

Main Methods:

  • Structural biology techniques (e.g., X-ray crystallography, cryo-EM) to determine the structures of Drosha-DGCR8 complexes with primary miRNAs.
  • Biochemical assays to study protein-RNA interactions and complex dynamics.
  • Comparative analysis of structural data from Microprocessor and Dicer homologs.

Main Results:

  • The structures reveal that RNA structural features, rather than sequence, form the basis for substrate recognition by Drosha-DGCR8.
  • Insights into the dynamic assembly and disassembly of the protein-RNA complex during miRNA processing.
  • Comparison with Dicer homologs highlights conserved and distinct mechanisms for RNA recognition.

Conclusions:

  • Microprocessor recognizes primary miRNAs based on their structural framework, ensuring accurate initiation of miRNA biogenesis.
  • Dynamic interactions within the Microprocessor complex are crucial for processing diverse RNA substrates.
  • Understanding these mechanisms provides a foundation for studying miRNA-related regulatory pathways and diseases.