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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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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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mTOR Contributes to the Proteome Diversity through Transcriptome-Wide Alternative Splicing.

Sze Cheng1, Naima Ahmed Fahmi2, Meeyeon Park1

  • 1Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Twin Cities, Minneapolis, MN 55445, USA.

International Journal of Molecular Sciences
|October 27, 2022
PubMed
Summary

Hyperactivation of the mTOR pathway triggers widespread exon skipping, generating shorter protein isoforms. This alternative splicing impacts protein function, stability, and modifications, revealing mTOR

Keywords:
alternative splicingfunctional proteomemTOR signalingpost-transcriptional gene regulation

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Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Genetics

Background:

  • The mammalian target of rapamycin (mTOR) pathway is integral to cellular processes like energy metabolism and proliferation.
  • Previous research demonstrated mTOR activation induces 3'-untranslated region (UTR) shortening via alternative polyadenylation, affecting the proteome.

Purpose of the Study:

  • To investigate the effects of mTOR hyperactivation on the transcriptome beyond 3'-UTR shortening.
  • To elucidate the role of alternative splicing (AS) in regulating the mTOR-controlled proteome.

Main Methods:

  • Transcriptome-wide analysis of gene expression following mTOR hyperactivation.
  • Identification and characterization of alternative splicing events, specifically exon skipping/exclusion.
  • Investigation of RNA processing factors, including SRSF3, involved in mTOR-mediated AS.

Main Results:

  • mTOR hyperactivation leads to transcriptome-wide exon skipping, producing shorter gene isoforms.
  • This widespread alternative splicing affects protein length, functional domains, half-life, and post-translational modifications.
  • SRSF3 was identified as a key RNA processing factor mediating mTOR-activated exon skipping.

Conclusions:

  • The mTOR pathway plays a significant role in regulating alternative splicing.
  • Widespread alternative splicing is a critical mechanism through which mTOR signaling modulates protein function and cellular processes.