The Rheumatologist
COVID-19 News
  • Connect with us:
  • Facebook
  • Twitter
  • LinkedIn
  • YouTube
  • Feed
  • Home
  • Conditions
    • Rheumatoid Arthritis
    • SLE (Lupus)
    • Crystal Arthritis
      • Gout Resource Center
    • Spondyloarthritis
    • Osteoarthritis
    • Soft Tissue Pain
    • Scleroderma
    • Vasculitis
    • Systemic Inflammatory Syndromes
    • Guidelines
  • Resource Centers
    • Axial Spondyloarthritis Resource Center
    • Gout Resource Center
    • Psoriatic Arthritis Resource Center
    • Rheumatoid Arthritis Resource Center
    • Systemic Lupus Erythematosus Resource Center
  • Drug Updates
    • Biologics & Biosimilars
    • DMARDs & Immunosuppressives
    • Topical Drugs
    • Analgesics
    • Safety
    • Pharma Co. News
  • Professional Topics
    • Ethics
    • Legal
    • Legislation & Advocacy
    • Career Development
      • Certification
      • Education & Training
    • Awards
    • Profiles
    • President’s Perspective
    • Rheuminations
    • Interprofessional Perspective
  • Practice Management
    • Billing/Coding
    • Quality Assurance/Improvement
    • Workforce
    • Facility
    • Patient Perspective
    • Electronic Health Records
    • Apps
    • Information Technology
    • From the College
    • Multimedia
      • Audio
      • Video
  • Resources
    • Issue Archives
    • ACR Convergence
      • Systemic Lupus Erythematosus Resource Center
      • Rheumatoid Arthritis Resource Center
      • Gout Resource Center
      • Abstracts
      • Meeting Reports
      • ACR Convergence Home
    • American College of Rheumatology
    • ACR ExamRheum
    • Research Reviews
    • ACR Journals
      • Arthritis & Rheumatology
      • Arthritis Care & Research
      • ACR Open Rheumatology
    • Rheumatology Image Library
    • Treatment Guidelines
    • Rheumatology Research Foundation
    • Events
  • About Us
    • Mission/Vision
    • Meet the Authors
    • Meet the Editors
    • Contribute to The Rheumatologist
    • Subscription
    • Contact
  • Advertise
  • Search
You are here: Home / Articles / Ro60 Autoantigen Regulates Inflammatory Gene Expression

Ro60 Autoantigen Regulates Inflammatory Gene Expression

November 9, 2015 • By Lara C. Pullen, PhD

  • Tweet
  • Email
Print-Friendly Version / Save PDF

Gio.tto_Shutterstock_DNASequence_500x270Systemic lupus erythematosus (SLE) is characterized by antibodies that target DNA and self-proteins. One such protein is the RNA binding protein Ro60. However, researchers have suspected that Ro60 is not just a passive target of autoantibodies, but may be an active regulator of the immune system and a direct contributor to SLE pathogenesis. New research reveals a link between the lupus autoantigen Ro60, Alu retroelements and type I interferon. The work by Tiffany Hung, PhD, a postdoctoral fellow at Genentech in San Francisco, and colleagues was published in the Oct. 23 issue of Science.1

You Might Also Like
  • Gene Expression Markers in T Cells Help Identify SLE Patient Subtypes
  • Switches That Regulate Gene Expression Offer Better Understanding of Rheumatic Disease Say Experts at the 2013 ACR/ARHP Annual Meeting
  • Gene Expression Signature Useful for Diagnosing Kawasaki Disease
Also By This Author
  • Lupus Flares Pose Greatest Risk for Adverse Pregnancy Outcomes in Women with SLE

The investigators began their study by evaluating two human cell lines and cataloging their Ro60-associated RNAs via individual nucleotide cross-linking and immunoprecipitation (iCLIP), followed by high-throughput sequencing. This process revealed that approximately two-thirds of the iCLIP tags localized to introns. When the researchers examined the shared iCLIP peaks for enriched motifs, they identified Y RNA consensus sequences, as well as a U-rich motif that corresponded to the 3′ antisense strand of an Alu element. They found the latter particularly intriguing because the Alu retroelement is a common repetitive transposable element in the human genome.

ad goes here:advert-1
ADVERTISEMENT
SCROLL TO CONTINUE

Next, Dr. Hung and colleagues tested the ability of radiolabeled Alu motif oligonucleotides to bind to purified recombinant Ro60. They confirmed that Ro60 did, indeed, bind to an RNA motif derived from endogenous Alu retroelements. To further investigate the functional role of Ro60, they created knockout cell lines containing undetectable levels of Ro60 protein and found that the absence of Ro60 led to an aberrant activation of inflammatory pathways.

The team next sought to determine if the widespread changes in gene expression in the knockout cells included alterations in Ro60-bound RNAs. This hypothesis was correct. They found the Ro60-knockout cell lines had enhanced expression of Alu RNAs, as well as increased activation of IFN-induced genes when compared with the parent cell line. Moreover, when the investigators isolated peripheral blood mononuclear lymphocytes (PBML) from healthy human donors, they found treatment of these cells with type I interferon induced Alu transcripts and stimulated the cells to secrete proinflammatory cytokines. When they transfected the PBMLs with synthesized RNAs, the Alu motif RNAs spontaneously stimulated secretion of multiple cytokines. In contrast, transfection with truncated Alu motifs resulted in submaximal cytokine responses.

ad goes here:advert-2
ADVERTISEMENT
SCROLL TO CONTINUE

The researchers next purified SLE serum immunoglobulin G (IgG) and found endogenous SLE IgGs also immunoprecipitated Alu transcripts and individuals with lupus had antibody-Ro60-Alu RNA immune complexes. Additionally, a test for Alu transcripts in blood cells of patients with SLE and controls revealed that Alu RNA was present at significantly higher levels in patients with SLE than in controls.

Pages: 1 2 | Single Page

Filed Under: Conditions, SLE (Lupus) Tagged With: Lupus, RNA, Ro60, systemic lupus erythematosus (SLE)

You Might Also Like:
  • Gene Expression Markers in T Cells Help Identify SLE Patient Subtypes
  • Switches That Regulate Gene Expression Offer Better Understanding of Rheumatic Disease Say Experts at the 2013 ACR/ARHP Annual Meeting
  • Gene Expression Signature Useful for Diagnosing Kawasaki Disease
  • Study Finds Correlations Between Synovial Tissue & Gene Expression

ACR Convergence

Don’t miss rheumatology’s premier scientific meeting for anyone involved in research or the delivery of rheumatologic care or services.

Visit the ACR Convergence site »

Meeting Abstracts

Browse and search abstracts from the ACR Convergence and ACR/ARP Annual Meetings going back to 2012.

Visit the Abstracts site »

Rheumatology Research Foundation

The Foundation is the largest private funding source for rheumatology research and training in the U.S.

Learn more »

The Rheumatologist newsmagazine reports on issues and trends in the management and treatment of rheumatic diseases. The Rheumatologist reaches 11,500 rheumatologists, internists, orthopedic surgeons, nurse practitioners, physician assistants, nurses, and other healthcare professionals who practice, research, or teach in the field of rheumatology.

About Us / Contact Us / Advertise / Privacy Policy / Terms of Use

  • Connect with us:
  • Facebook
  • Twitter
  • LinkedIn
  • YouTube
  • Feed

Copyright © 2006–2022 American College of Rheumatology. All rights reserved.

ISSN 1931-3268 (print)
ISSN 1931-3209 (online)

loading Cancel
Post was not sent - check your email addresses!
Email check failed, please try again
Sorry, your blog cannot share posts by email.