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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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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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Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
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Using the E1A Minigene Tool to Study mRNA Splicing Changes
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SRC Kinase Isoforms Regulate mRNA Splicing during Neural Development.

Alastair R Pizzey1, Laura C West1, Samuel J Elberfeld1

  • 1Department of Biology and York Biomedical Research Institute, University of York, Heslington, York YO10 5DD, United Kingdom.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|August 1, 2025
PubMed
Summary
This summary is machine-generated.

The neural-specific N1-SRC kinase regulates alternative mRNA splicing during embryonic development. This process is crucial for neurogenesis by controlling splicing factors like HNRNPA1 and TRA2A.

Keywords:
SRCXenopusneurogenesisphosphorylationtyrosine kinase

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Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Neuroscience

Background:

  • Alternative mRNA splicing drives transcriptomic diversity for tissue-specific functions.
  • Master regulators of alternative splicing during embryonic brain development are largely unknown.
  • Neural-specific N1-SRC kinase, generated by splicing of C-SRC, is critical for neurogenesis.

Purpose of the Study:

  • To elucidate the targets and mechanism of N1-SRC in regulating neurogenesis.
  • To investigate the role of N1-SRC in controlling the alternative splicing landscape.
  • To understand how N1-SRC influences splicing regulators during neuronal differentiation.

Main Methods:

  • Screening for N1-SRC SH3 domain interactors.
  • Analysis of public phosphoproteomic data for SRC-dependent phosphorylation.
  • Long- and short-read RNA sequencing of N1-SRC knockdown *Xenopus* embryos.

Main Results:

  • N1-SRC SH3 domain interactors are enriched in splicing regulators.
  • SRC-dependent phosphorylation of splicing machinery, including RNA-binding proteins (RBPs), is widespread.
  • N1-SRC knockdown leads to aberrant splicing of splicing regulators HNRNPA1 and TRA2A.
  • A proposed mechanism involves N1-SRC regulating splicing factors SFPQ and FUS, which in turn affect HNRNPA1 and TRA2A splicing.

Conclusions:

  • The neuronal splicing of C-SRC to N1-SRC is a key regulator of the alternative splicing landscape during neurogenesis.
  • N1-SRC controls neurogenesis by modulating the splicing of critical splicing factors.
  • This study reveals a novel regulatory pathway linking tyrosine kinase activity to alternative splicing in neural development.