Retro (2016) week 40 - I - ADAR1 restricts LINE-1 retrotransposition
Title
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ADAR1 restricts LINE-1 retrotransposition
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Main Authors
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Elisa Orecchini; Alessandro Michienzi
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Main institution
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University of Rome ‘Tor Vergata’
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Read
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September 30, 2016
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Link to the manuscript
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Notes
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Intro:
RNA editing proteins (ADARs) can restrict (antiviral) or be exploited (proviral) by (endogenous and exogenous) virus.
Vesicular stomatitis virus (6,7), hepatitis D virus (8), dengue virus (9), human T-cell leukemia virus type 1 and type 2 (10) and many other viruses (5)
Lymphocytic choriomeningitis virus (11), bovine viral diarrhea virus (12) and hepatitis C virus (13)
Results:
ADAR1 is associated with many protein related to the regulation of L1 activity. Namely Orecchini et al tested the interactions between ADAR1 and:
- NCL;
- hnRNP L;
- HSPA1A;
- PABPC1;
- PSF;
- NONO
Next Orecchini et al tested if the knock out of ADAR1 influences the retrotransposition of L1s and found that "knockdown of ADAR1 expression in HeLa cells increased L1 activity by 2- to 3-fold when compared to controls (scramble shRNA and empty vector)". Other vectors were tested and similar results were found. "Knockdown of ADAR1 expression in HeLa cells increased L1 retrotransposition efficiency by at least 6-fold when compared to the controls."
Over expression of ADAR1 results is less ensuring. From Figure5, we can learn that the empty vector is over expressed, the Fluc/Rluc ration is 0.025, or 2.5%. Which in turn could be roughly interpreted as “the proportion of transfected vectors mobilized". When ADAR1 is over-expressed, the Fluc/Rluc is reduced to 1% or .5%. Indeed, there is a reduction of about 50%, however, both are extremely small proportions.
From Co-immunopreciptation Orecchini learn that:
"ADAR1 may affect L1 retrotransposition by binding the basal L1 RNP complex." There it binds to both L1 ORF1 (not the reverse transcriptase) and L1 transcripts. On other hand, the extracted L1 mRNA do not show signal of RNA edition. But further experiments should be performed to rule out the editing of L1 mRNAs.
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