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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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During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
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In eukaryotic cells, transcripts made by RNA polymerase are modified and processed before exiting the nucleus. Unprocessed RNA is called precursor mRNA or pre-mRNA to distinguish it from mature mRNA.
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Using the E1A Minigene Tool to Study mRNA Splicing Changes
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Betacoronavirus-specific alternate splicing.

Guy Karlebach1,2, Bruce Aronow2,3, Stephen B Baylin2,4

  • 1The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA.

Biorxiv : the Preprint Server for Biology
|July 7, 2021
PubMed
Summary

SARS-CoV-2 and related coronaviruses alter cellular mRNA splicing, impacting diverse genes and functions. These viral infections show distinct splicing patterns, including intron retention and pseudouridine modifications, affecting ribosomal genes.

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Area of Science:

  • Molecular Biology
  • Virology
  • Genomics

Background:

  • Viruses, including SARS-CoV-2, can disrupt host cell processes to evade innate immunity.
  • Viral interactions with cellular splicing machinery are known, with SARS-CoV-2 suppressing global mRNA splicing.

Approach:

  • Analyzed 17 datasets from SARS-CoV-2, SARS-CoV, MERS, and other pathogens (Streptococcus pneumonia, HCV, Zika, Dengue, influenza, RSV).
  • Investigated differential alternative splicing (DAS) and differential gene expression (DGE) patterns.

Key Points:

  • SARS-CoV-2, SARS-CoV, and MERS exhibit similar functional profiles in differentially spliced genes.
  • Coronavirus-infected cells show increased intron retention, pseudouridine modification, and fewer exons in spliced transcripts.
  • Viral load in COVID-19 patients correlates with altered isoform distribution.
  • Betacoronavirus infections disproportionately affect ribosomal genes and show depletion of RNA-binding protein sites.

Conclusions:

  • Identified characteristic differential splicing patterns in SARS-CoV-2, SARS-CoV, and MERS infections.
  • These splicing alterations potentially modify a broad range of cellular functions and genes crucial for viral biology.