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Related Concept Videos

MicroRNAs01:22

MicroRNAs

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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...
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Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
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Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
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Related Experiment Video

Updated: Mar 8, 2026

Identifying Dysregulated Genes Induced by Kaposi's Sarcoma-associated Herpesvirus KSHV
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Identifying Dysregulated Genes Induced by Kaposi's Sarcoma-associated Herpesvirus KSHV

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KSHV SOX mediated host shutoff: the molecular mechanism underlying mRNA transcript processing.

Hyunah Lee1,2, Anathe O M Patschull1, Claire Bagnéris1

  • 1Institute for Structural and Molecular Biology, Department of Biological Sciences, Birkbeck College, Malet Street, London WC1E 7HX, UK.

Nucleic Acids Research
|January 30, 2017
PubMed
Summary

The KSHV SOX enzyme degrades host mRNA during viral infection. Structural and biochemical studies reveal how SOX binds and degrades RNA, working with Xrn1 to shut off host gene expression.

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Analysis of Group IV Viral SSHHPS Using In Vitro and In Silico Methods
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Analysis of Group IV Viral SSHHPS Using In Vitro and In Silico Methods

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Area of Science:

  • Virology
  • Molecular Biology
  • Structural Biology

Background:

  • Kaposi's sarcoma-associated herpesvirus (KSHV) infection involves a lytic phase characterized by host shutoff.
  • Host shutoff is mediated by the viral SOX (SOP-associated exonuclease) enzyme, which degrades host and viral mRNA.
  • The precise RNA structures targeted by SOX and its mechanism of action were not fully understood.

Purpose of the Study:

  • To elucidate the RNA structural elements targeted by the KSHV SOX enzyme.
  • To determine the crystal structure of SOX bound to an RNA substrate.
  • To investigate the coordinated roles of SOX and host factors in mRNA degradation.

Main Methods:

  • Bioinformatic analysis of KSHV target transcripts.
  • In vitro degradation assays using purified SOX and RNA fragments.
  • X-ray crystallography to determine the SOX-RNA complex structure.
  • Biochemical and biophysical characterization of SOX activity.

Main Results:

  • Identification of common structural motifs in SOX-targeted RNA transcripts.
  • Determination of the crystal structure of SOX bound to a KSHV K12-2 RNA fragment.
  • Elucidation of structural determinants for RNA recognition and cleavage by SOX.
  • Confirmation of SOX and host exoribonuclease Xrn1 acting in concert for mRNA degradation.

Conclusions:

  • SOX targets specific RNA structures for degradation during KSHV host shutoff.
  • The crystal structure provides insights into SOX's RNA binding and catalytic mechanisms.
  • SOX and Xrn1 collaborate to efficiently degrade mRNA, contributing to the viral life cycle.