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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...
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...
Regulation of Hematopoietic Stem Cells01:01

Regulation of Hematopoietic Stem Cells

All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
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The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
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Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.

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Genome-wide Analysis of HDAC Inhibitor-mediated Modulation of microRNAs and mRNAs in B Cells Induced to Undergo Class-switch DNA Recombination and Plasma Cell Differentiation
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Glucocorticoids modulate microRNA expression and processing during lymphocyte apoptosis.

Lindsay K Smith1, Ruchir R Shah, John A Cidlowski

  • 1Molecular Endocrinology Group, Laboratory of Signal Transduction, NIEHS, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina 27709, USA.

The Journal of Biological Chemistry
|September 18, 2010
PubMed
Summary

Glucocorticoids repress microRNAs (miRNAs) and key processing enzymes, leading to lymphocyte apoptosis. Restoring miRNA processing or inhibiting specific miRNAs can influence cell death decisions.

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Genome-wide Analysis of HDAC Inhibitor-mediated Modulation of microRNAs and mRNAs in B Cells Induced to Undergo Class-switch DNA Recombination and Plasma Cell Differentiation
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Published on: February 20, 2015

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Glucocorticoids regulate immune cells and induce lymphocyte apoptosis through gene expression changes.
  • MicroRNAs (miRNAs) are critical regulators of lymphocyte function, but their role in glucocorticoid-induced apoptosis is unclear.

Purpose of the Study:

  • To investigate whether glucocorticoids regulate miRNAs during lymphocyte apoptosis.
  • To determine if altered miRNA processing contributes to glucocorticoid-induced lymphocyte cell death.

Main Methods:

  • Microarray and deep sequencing analysis of primary rat thymocytes undergoing glucocorticoid-induced apoptosis.
  • Quantitative analysis of microRNA transcripts and key processing enzyme expression (Dicer, Drosha, DGCR8/Pasha).
  • Dicer silencing in human leukemic cell lines and overexpression of the miR-17-92 polycistron.

Main Results:

  • MicroRNAs were significantly repressed during glucocorticoid-induced thymocyte apoptosis.
  • Expression of Dicer, Drosha, and DGCR8/Pasha was reduced at both mRNA and protein levels.
  • Dicer depletion enhanced glucocorticoid-induced apoptosis, while miR-17-92 overexpression blunted it.

Conclusions:

  • Glucocorticoids alter post-transcriptional miRNA expression by repressing the miRNA bioprocessing pathway.
  • MicroRNA processors and specific miRNAs play a role in glucocorticoid-mediated lymphocyte cell fate decisions.