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Related Concept Videos

Alternative RNA Splicing02:18

Alternative RNA Splicing

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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.
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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...
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In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
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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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During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
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Updated: Jul 8, 2025

A Reporter Based Cellular Assay for Monitoring Splicing Efficiency
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Argonaute3-SF3B3 complex controls pre-mRNA splicing to restrain type 2 immunity.

Riccardo Guidi1, Christopher Wedeles1, Daqi Xu1

  • 1Immunology Discovery, Genentech, South San Francisco, CA 94080, USA.

Cell Reports
|December 14, 2023
PubMed
Summary
This summary is machine-generated.

Argonaute proteins AGO1, AGO3, and AGO4 are not essential for microRNA function but regulate T helper cell immunity through mRNA splicing. They interact with the spliceosome to control gene expression and inflammatory responses.

Keywords:
CP: ImmunologyCP: Molecular biologyIL-13RNAiT cellT(H)2allergyeosinophilgene regulationhelminthlymphocytemiRNA

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Using the E1A Minigene Tool to Study mRNA Splicing Changes
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Using the E1A Minigene Tool to Study mRNA Splicing Changes

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Area of Science:

  • Molecular Biology
  • Immunology
  • Genetics

Background:

  • Argonaute (AGO) proteins are key mediators of microRNA (miRNA)-guided gene silencing.
  • The specific roles of all four mammalian AGO proteins (AGO1-4) in miRNA activity and other cellular processes remain incompletely understood.

Purpose of the Study:

  • To investigate the distinct functions of AGO proteins beyond canonical miRNA-mediated gene silencing.
  • To determine the requirement of AGO1, AGO3, and AGO4 in miRNA activity and immune cell function.

Main Methods:

  • Generation and analysis of Ago1, Ago3, and Ago4-deficient mice (Ago134Δ).
  • Gain- and loss-of-function experiments in CD4+ T helper lymphocytes.
  • Co-immunoprecipitation assays to identify protein interactions.

Main Results:

  • AGO1, AGO3, and AGO4 are redundant for miRNA biogenesis and function, with AGO2 fulfilling this role.
  • AGO1/3/4 are crucial for regulating type 2 immunity expansion through precursor mRNA splicing in CD4+ T helper cells.
  • Nuclear AGO3 directly interacts with SF3B3, a spliceosome component, to regulate global mRNA splicing and Nisch gene isoforms.

Conclusions:

  • AGO1, AGO3, and AGO4 are uncoupled from miRNA-mediated RNA interference.
  • A novel AGO3:SF3B3 nuclear complex involved in mRNA splicing and immune regulation is identified.
  • This study reveals a new mechanism for AGO protein involvement in inflammatory diseases through spliceosome modulation.