Intestinal Epithelial Cell-Related Alternative Splicing Events in Dextran Sodium Sulfate-Induced Acute Colitis

    Abstract

    Insights

    This study identified 340 alternative splicing events in mouse models of acute colitis, revealing their role in apoptosis and potential impact on inflammatory bowel disease pathogenesis.

    Area of Science:

    • Molecular Biology
    • Genomics
    • Disease Pathogenesis

    Background:

    • Alternative splicing of pre-messenger RNA is vital for gene expression regulation and proteome diversity.
    • Alternative splicing is implicated in the pathogenesis of inflammatory bowel disease (IBD).

    Purpose of the Study:

    • To identify alternative splicing events in intestinal epithelial cells during acute colitis in mice.
    • To enhance understanding of the molecular mechanisms underlying IBD pathogenesis.

    Main Methods:

    • Acute colitis mouse models were established, and colon intestinal epithelial cells were isolated for RNA sequencing.
    • Multivariate Analysis of Transcript Splicing software analyzed alternative splicing events.
    • Functional analysis and reverse transcription polymerase chain reaction (RT-PCR) validated key findings.

    Main Results:

    • 340 significant differential alternative splicing events (from 293 genes) were identified in acute colitis.
    • Validated alternative splicing events in CDK5 and TRM5 genes.
    • Functional analysis indicated involvement in apoptotic processes, with validation for BCL2/E1B, TRAF1, and TRAF7.

    Conclusions:

    • Differential alternative splicing plays a significant role in acute colitis.
    • These findings highlight the potential impact of alternative splicing on IBD pathogenesis.

    Related Concept Videos

    Alternative RNA Splicing02:18

    Alternative RNA Splicing

    Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
    There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
    21.5K
    RNA Splicing01:32

    RNA Splicing

    Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
    56.5K
    Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

    Role Of Notch Signalling In Intestinal Stem Cell Renewal

    Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
    Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
    2.1K
    Renewal of Intestinal Stem Cells01:23

    Renewal of Intestinal Stem Cells

    The intestinal epithelial lining rapidly renews every 4 to 5 days. The renewal is facilitated by intestinal stem cells (ISCs) located at the base of the crypt– a gland located at the bottom of each villus. ISCs divide asymmetrically to form new stem cells and progenitor daughter cells. The daughter cells are called transit-amplifying (TA) cells which move upwards along the crypt and either differentiate into absorptive cells– the enterocytes or secretory cells– including the...
    2.6K
    Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

    Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

    Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
    2.3K