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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.
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...
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RNA Splicing01:32

RNA Splicing

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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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Chromatin Structure Regulates pre-mRNA Processing02:41

Chromatin Structure Regulates pre-mRNA Processing

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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.
The chromatin structure, especially...
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Ligand Binding and Linkage00:49

Ligand Binding and Linkage

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Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked.  In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
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Leaky Scanning02:28

Leaky Scanning

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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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What is Gene Expression?01:36

What is Gene Expression?

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A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is comprised  of nucleotides and proteins are comprised of amino acids, a mediator is required to convert the information encoded in DNA into proteins. This mediator is the messenger RNA (mRNA). mRNA copies the blueprint from DNA by a process called transcription. In eukaryotes, transcription occurs in the nucleus by complementary base-pairing with the DNA template. The mRNA is then...
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Detection of Alternative Splicing During Epithelial-Mesenchymal Transition
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Histamine H3 Receptor Isoforms: Insights from Alternative Splicing to Functional Complexity.

Meichun Gao1, Jasper F Ooms1, Rob Leurs1

  • 1Amsterdam Institute of Molecular and Life Sciences, Division of Medicinal Chemistry, Faculty of Science, Vrije Universiteit Amsterdam, 1081 HZ Amsterdam, The Netherlands.

Biomolecules
|July 27, 2024
PubMed
Summary

Alternative splicing creates diverse histamine H3 receptor (H3R) isoforms, impacting central nervous system function. Understanding these H3R variants is key for developing targeted therapies for neurological disorders.

Keywords:
RNA sequencingdimerizationhistamine H3 receptorisoformsignaling

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Quantitative Analysis of Alternative Pre-mRNA Splicing in Mouse Brain Sections Using RNA In Situ Hybridization Assay
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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pharmacology

Background:

  • Alternative splicing of G protein-coupled receptors (GPCRs), including the histamine H3 receptor (H3R), generates multiple isoforms.
  • These H3R isoforms possess potentially distinct pharmacological and physiological properties.
  • The functional significance of numerous H3R isoforms remains largely unknown despite their role in neurotransmitter release.

Purpose of the Study:

  • To review the complexity of H3R isoforms and their potential roles in central nervous system (CNS) function.
  • To highlight the importance of understanding H3R isoform functionality for targeted therapeutic development.

Main Methods:

  • Review of recent RNA sequencing data confirming H3R isoform expression in the brain.
  • Comparative analysis of H3R splicing across species to understand evolutionary conservation and divergence.
  • Discussion of potential isoform-specific functions and interactions within neural circuits.

Main Results:

  • Multiple H3R isoforms are expressed in the brain, with some showing unique tissue-specific distribution.
  • Evolutionary analysis reveals conserved and divergent H3R splicing patterns across species, indicating varied regulatory mechanisms.
  • The functional roles of these H3R isoforms are not yet fully elucidated.

Conclusions:

  • Understanding H3R isoform complexity is critical for advancing the treatment of neurological and psychiatric disorders.
  • Knowledge of H3R isoform functionality will enable the design of more precise pharmacological interventions.
  • Targeted therapeutics based on H3R isoform specificity could improve efficacy and reduce side effects.