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RNA Splicing01:32

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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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The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
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Determining Genome-wide Transcript Decay Rates in Proliferating and Quiescent Human Fibroblasts
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Alternative splicing coupled mRNA decay shapes the temperature-dependent transcriptome.

Alexander Neumann1,2, Stefan Meinke1, Gesine Goldammer1

  • 1Institute of Chemistry and Biochemistry, Laboratory of RNA Biochemistry, Freie Universität Berlin, Berlin, Germany.

EMBO Reports
|November 3, 2020
PubMed
Summary
This summary is machine-generated.

Body temperature influences gene expression through alternative splicing (AS) and mRNA decay. This ancient mechanism, conserved across species, regulates daily rhythms in gene expression independently of the core clock.

Keywords:
NMDSR proteinsalternative splicingcircadian clockmRNA decaytemperature

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Area of Science:

  • Molecular Biology
  • Genetics
  • Chronobiology

Background:

  • Mammalian body temperature exhibits daily oscillations and is affected by disease.
  • A previously identified kinase regulates alternative splicing (AS) in response to body temperature.
  • Alternative splicing can produce non-productive mRNA variants targeted for degradation by pathways like nonsense-mediated decay (NMD).

Purpose of the Study:

  • To investigate the link between body temperature-controlled alternative splicing and mRNA decay.
  • To elucidate the role of this coupling in regulating temperature-dependent gene expression.
  • To determine if this mechanism is conserved and contributes to rhythmic gene expression.

Main Methods:

  • Analysis of temperature-controlled alternative splicing events.
  • Investigation of mRNA decay pathways, including NMD.
  • Examination of gene expression profiles in response to temperature changes in mammals and plants.

Main Results:

  • Body temperature-controlled alternative splicing is extensively coupled to mRNA decay, globally regulating gene expression.
  • Temperature-sensitive splicing events that induce decay are evolutionarily conserved, particularly in RNA-binding proteins like SR proteins.
  • Alternative splicing-coupled poison exon inclusion is crucial for the rhythmic gene expression of SR proteins and establishes temperature-dependent rhythmic gene expression patterns.

Conclusions:

  • Body temperature-driven alternative splicing coupled with mRNA decay is an ancient mechanism for generating rhythmic gene expression.
  • This process operates independently of the core biological clock.
  • The findings reveal a fundamental link between temperature, splicing, decay, and circadian or daily gene expression rhythms.