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Related Concept Videos

Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

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Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
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Integrins01:10

Integrins

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Animal and protozoan cells do not have cell walls to help maintain shape and provide structural stability. Instead, these eukaryotic cells secrete a sticky mass of carbohydrates and proteins into the spaces between adjacent cells. This network of proteins and molecules is called an extracellular matrix or ECM.
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Integrator and Differentiator01:13

Integrator and Differentiator

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Op-amp circuits have significant applications in various fields, including automotive engineering. One such application is cruise control systems in cars, where op-amp circuits are integral for maintaining a constant speed. In these systems, op-amps function as both integrators and differentiators.
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Activation of Integrins01:15

Activation of Integrins

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Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...
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IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

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Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
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Protein Transport to the Inner Chloroplast Membrane01:18

Protein Transport to the Inner Chloroplast Membrane

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Proteins targeted to the inner chloroplast membrane, or plastid proteins, are transported by two general pathways: the stop-transfer and the re-insertion or post-import pathways. Most plastid proteins carry N-terminal transit sequences and internal import sequences targeting it to the specific chloroplast subcompartment. Proteins targeted by the stop-transfer pathway have internal hydrophobic sequences that inhibit their translocation into the stroma. As a result, these precursors are arrested...
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Updated: Aug 27, 2025

Preparation of Quality Inositol Pyrophosphates
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Inositol hexakisphosphate is required for Integrator function.

Min-Han Lin1, Madeline K Jensen2,3, Nathan D Elrod2

  • 1Department of Biological Sciences, Columbia University, New York, NY, 10027, USA.

Nature Communications
|September 30, 2022
PubMed
Summary
This summary is machine-generated.

Inositol hexakisphosphate (IP6) is essential for the Integrator complex's function in RNA processing and transcription attenuation. This discovery, supported by structural and functional studies, highlights IP6's conserved role across species.

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Absolute Quantitation of Inositol Pyrophosphates by Capillary Electrophoresis Electrospray Ionization Mass Spectrometry
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Absolute Quantitation of Inositol Pyrophosphates by Capillary Electrophoresis Electrospray Ionization Mass Spectrometry
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Area of Science:

  • Molecular Biology
  • Structural Biology
  • Biochemistry

Background:

  • The Integrator complex, associated with RNA polymerase II, regulates noncoding RNA 3'-end processing and mRNA transcription attenuation.
  • IntS11 acts as the endonuclease within the Integrator cleavage module (ICM).

Purpose of the Study:

  • To elucidate the structural basis of Integrator complex function.
  • To investigate the role of inositol hexakisphosphate (IP6) in Integrator activity.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) to determine the structure of the Drosophila ICM at 2.74 Å resolution.
  • Biochemical assays to identify and characterize the IP6 binding site.
  • Functional assays in Drosophila and human cells to assess the impact of IP6 binding site mutations and IP6 biosynthesis disruption on Integrator function.

Main Results:

  • The cryo-EM structure revealed a stable association of inositol hexakisphosphate (IP6) within a conserved electropositive pocket at the interface of the IntS4-IntS9-IntS11 ICM subunits.
  • IP6 binding was confirmed in both Drosophila and human ICM, located 55 Å from the IntS11 active site.
  • Mutations in the IP6 binding site or disruption of IP6 biosynthesis significantly impaired Integrator function in snRNA 3'-end processing and mRNA transcription attenuation.

Conclusions:

  • Inositol hexakisphosphate (IP6) is a critical cofactor for the Integrator complex.
  • IP6 is required for both noncoding RNA 3'-end processing and mRNA transcription attenuation.
  • The findings suggest a conserved requirement for IP6 in Integrator function across different organisms, including Drosophila and humans.