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Related Concept Videos

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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Chromatin Structure Regulates pre-mRNA Processing02:41

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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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Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
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A Reporter Based Cellular Assay for Monitoring Splicing Efficiency
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Splicing-accessible coding 3'UTRs control protein stability and interaction networks.

Marco Preussner1, Qingsong Gao2, Eliot Morrison3

  • 1Institute of Chemistry and Biochemistry, Freie Universität Berlin, Laboratory of RNA Biochemistry, Takustrasse 6, 14195, Berlin, Germany.

Genome Biology
|July 31, 2020
PubMed
Summary
This summary is machine-generated.

A newly discovered protein-coding function of 3' untranslated regions (3'UTRs) involves frameshift-inducing alternative splicing. This mechanism, found in over 10% of genes, impacts protein interactions and stability.

Keywords:
3′UTRAlternative open reading frameAlternative splicingGenome structureProtein disorderProtein stabilityProtein-protein interaction

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Area of Science:

  • Genetics
  • Molecular Biology
  • Proteomics

Background:

  • 3' untranslated regions (3'UTRs) are known regulators of mRNA metabolism, affecting stability, translation, and localization.
  • The significant length of some 3'UTRs compared to coding regions suggests undiscovered functions.
  • This study investigates a novel protein-coding role for 3'UTRs.

Purpose of the Study:

  • To identify and characterize the protein-coding potential of 3'UTRs.
  • To understand the functional implications of 3'UTR translation.
  • To explore the role of this mechanism in gene regulation and disease.

Main Methods:

  • Analysis of frameshift-inducing alternative splicing events in human and mouse genomes.
  • Characterization of amino acid sequences encoded by 3'UTRs.
  • Investigation of protein-protein interactions and stability of 3'UTR-encoded proteins.

Main Results:

  • Frameshift-inducing alternative splicing enables protein-coding in over 10% of human and mouse genes via their 3'UTRs.
  • 3'UTR-encoded sequences are enriched in PxxP motifs, influencing protein disorder and stability.
  • This mechanism can regulate protein half-life and potentially act as a surveillance system for aberrant splicing.

Conclusions:

  • A conserved mechanism enriches the mammalian proteome through 3'UTR translation.
  • This process controls protein expression and protein-protein interactions.
  • Findings have significant implications for identifying novel protein variants and understanding disease mechanisms.