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Related Concept Videos

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.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
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RNA Splicing01:32

RNA Splicing

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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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Leaky Scanning02:28

Leaky Scanning

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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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RNA Editing02:23

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RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...
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Pre-mRNA Processing: Modification of pre-mRNA Ends01:35

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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.
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a cap to the 5' end of the growing transcript. In this process, a 5' phosphate is replaced by modified guanosine that has a methyl group attached (7-methyl guanosine). This 5' cap helps...
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Updated: Oct 5, 2025

Using the E1A Minigene Tool to Study mRNA Splicing Changes
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Betacoronavirus-specific alternate splicing.

Guy Karlebach1, Bruce Aronow2, Stephen B Baylin3

  • 1The Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington 06032, CT, USA; COVID-19 International Research Team.

Genomics
|January 25, 2022
PubMed
Summary

SARS-CoV-2 and other betacoronaviruses alter cellular splicing, impacting diverse genes and functions. These viral infections lead to specific splicing patterns, including intron retention and changes in ribosomal genes, affecting cellular processes and antiviral responses.

Keywords:
Alternative splicingBetacoronavirusCOVID-19Gene regulationSARS-CoV-2

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Area of Science:

  • Molecular Biology
  • Virology
  • Genomics

Background:

  • Viruses, including SARS-CoV-2, manipulate host cell processes like mRNA splicing to evade antiviral defenses.
  • SARS-CoV-2 infection globally suppresses mRNA splicing, with viral proteins interacting with human RNAs.

Purpose of the Study:

  • To investigate differential alternative splicing patterns in SARS-CoV-2 infection across multiple datasets.
  • To compare splicing changes induced by SARS-CoV-2 with those caused by other coronaviruses (SARS-CoV, MERS) and other viruses.
  • To identify characteristic splicing alterations and their functional consequences during betacoronavirus infections.

Main Methods:

  • Analysis of 17 experimental and clinical datasets related to SARS-CoV-2, SARS-CoV, MERS, and other viral infections.
  • Comparative analysis of differentially spliced genes and their functional profiles.
  • Examination of transcript features like intron retention, pseudouridine modification, and exon number.
  • Correlation of viral load with isoform distribution in clinical samples.
  • Assessment of ribosomal gene involvement and RNA-binding protein interactions.

Main Results:

  • Genes with differential alternative splicing in SARS-CoV-2 share functional profiles with those in SARS-CoV and MERS infections.
  • Differentially spliced transcripts in coronavirus infections show increased intron retention, pseudouridine modification, and fewer exons.
  • Viral load in COVID-19 patients correlates with the distribution of alternatively spliced isoforms.
  • Betacoronavirus infections significantly affect ribosomal genes and show depletion of RNA-binding protein sites in affected genes.

Conclusions:

  • SARS-CoV-2, SARS-CoV, and MERS infections exhibit characteristic differential splicing patterns.
  • Alternative splicing changes during betacoronavirus infections broadly modify cellular functions by altering gene product activities.
  • These splicing alterations are a key mechanism by which viruses impact host cell biology and antiviral responses.