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Related Concept Videos

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Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
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Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
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The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
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The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
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DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
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Related Experiment Video

Updated: May 26, 2025

In Vitro Differentiation Model of Human Normal Memory B Cells to Long-lived Plasma Cells
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m6A eraser ALKBH5/treRNA1/DDX46 axis regulates BCR expression.

Bandish Kapadia1, Anirban Roychowdhury1, Forum Kayastha1

  • 1Division of Hematology, Oncology, and Palliative Care, Department of Internal Medicine, School of Medicine, Virginia Commonwealth University, Richmond, VA, USA; Section of Hematology and Oncology, Medicine Service, Richmond VA Cancer Center, Richmond Veteran Affairs Medical Center, Richmond, VA, USA; VCU Massey Comprehensive Cancer Center, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298, USA.

Neoplasia (New York, N.Y.)
|February 23, 2025
PubMed
Summary
This summary is machine-generated.

The study found that the ALKBH5-treRNA1-DDX46 complex removes N6-methyladenosine (m6A) marks from RNA, enhancing B-cell receptor signaling. This epitranscriptomic regulation is crucial for B-cell function and offers therapeutic targets.

Keywords:
ALKBH5B-cell receptor signalingDDX46EpitranscriptomicsImmune regulationN6-methyladenosine (m6A)Oncogenic pathwaysRNA demethylationtreRNA1

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Area of Science:

  • Epitranscriptomics
  • Molecular Biology
  • Immunology

Background:

  • N6-methyladenosine (m6A) modifications regulate RNA processing and are vital in B-cell immunity and cancer.
  • ALKBH5 is a key RNA demethylase, but its role in B-cell receptor (BCR) signaling remains unclear.

Purpose of the Study:

  • To investigate the role of m6A demethylation in BCR signaling pathways.
  • To identify novel regulators involved in m6A removal within B-cells.

Main Methods:

  • Investigated the interaction between ALKBH5, treRNA1 (Translation Regulatory Long Non-Coding RNA 1), and DDX46 (RNA helicase) in B-cells.
  • Analyzed the impact of m6A demethylation on BCR signaling pathway transcripts.
  • Assessed the effects of disrupting the ALKBH5-treRNA1-DDX46 axis on B-cell function.

Main Results:

  • A novel complex of ALKBH5, treRNA1, and DDX46 was identified, which translocates to the nucleus upon activation.
  • This complex removes m6A marks from BCR signaling-related transcripts, enhancing their stability and translation via HuR.
  • Loss of ALKBH5, treRNA1, or DDX46 impaired RNA processing and reduced BCR gene expression.

Conclusions:

  • The ALKBH5-treRNA1-DDX46 complex plays a critical role in B-cell functionality by regulating RNA dynamics through m6A demethylation.
  • This epitranscriptomic mechanism is essential for maintaining proper BCR signaling and offers potential therapeutic targets for immune disorders and cancer.