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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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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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The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes. 
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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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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
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Shaping human brain development and vulnerability through alternative splicing.

Francisco Aya1, Juan Valcárcel2

  • 1Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain; Department of Medical Oncology, IDIBAPS, Hospital Clinic, Barcelona, Spain.

Cell Genomics
|June 13, 2024
PubMed
Summary
This summary is machine-generated.

The RNA-binding protein MBNL2 regulates Tau splicing isoforms in the brain across primates. This differential regulation impacts Tau protein aggregation and neurodegeneration in humans.

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Area of Science:

  • Genomics
  • Neuroscience
  • Molecular Biology

Background:

  • Alternative splicing generates diverse protein isoforms, influencing cell function and phenotypes.
  • Microtubule-associated protein Tau (Tau) splicing is critical for neuronal function.
  • Dysregulation of Tau is implicated in neurodegenerative diseases.

Purpose of the Study:

  • To investigate the role of RNA-binding proteins in regulating Tau splicing across primate species.
  • To understand the evolutionary basis of Tau splicing differences.
  • To explore the link between Tau splicing, protein aggregation, and human neurodegeneration.

Main Methods:

  • Comparative analysis of Tau splicing patterns in primate brain tissues.
  • RNA-binding protein immunoprecipitation (RIP) assays to identify MBNL2 targets.
  • In vitro and in vivo experiments to assess the functional impact of MBNL2 on Tau splicing and aggregation.

Main Results:

  • The RNA-binding protein MBNL2 differentially regulates Tau splicing isoforms in primate brains.
  • Specific Tau isoforms influenced by MBNL2 are associated with altered protein aggregation.
  • Human Tau splicing patterns, regulated by MBNL2, correlate with increased neurodegeneration risk.

Conclusions:

  • MBNL2 plays a key role in primate-specific regulation of Tau splicing.
  • Differential Tau splicing contributes to species-specific differences in Tau aggregation and neurodegeneration.
  • Understanding MBNL2-mediated Tau splicing offers insights into human neurodegenerative diseases.