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Determining 3'-Termini and Sequences of Nascent Single-Stranded Viral DNA Molecules during HIV-1 Reverse Transcription in Infected Cells
Published on: January 30, 2019
Comparison of cellular ribonucleoprotein complexes associated with the APOBEC3F and APOBEC3G antiviral proteins
Sarah Gallois-Montbrun1, Rebecca K Holmes, Chad M Swanson
1Department of Infectious Diseases, King's College London School of Medicine, London SE1 9RT, United Kingdom.
Abstract:
The human apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3F (APOBEC3F [A3F]) and A3G proteins are effective inhibitors of infection by various retroelements and share approximately 50% amino acid sequence identity. We therefore undertook comparative analyses of the protein and RNA compositions of A3F- and A3G-associated ribonucleoprotein complexes (RNPs). Like A3G, A3F is found associated with a complex array of cytoplasmic RNPs and can accumulate in RNA-rich cytoplasmic microdomains known as mRNA processing bodies or stress granules. While A3F RNPs display greater resistance to disruption by RNase digestion, the major protein difference is the absence of the Ro60 and La autoantigens. Consistent with this, A3F RNPs also lack a number of small polymerase III RNAs, including the RoRNP-associated Y RNAs, as well as 7SL RNA. Alu RNA is, however, present in A3F and A3G RNPs, and both proteins suppress Alu element retrotransposition. Thus, we define a number of subtle differences between the RNPs associated with A3F and A3G and speculate that these contribute to functional differences that have been described for these proteins.
Insights
Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3F (APOBEC3F) and A3G proteins, crucial for retroelement inhibition, exhibit distinct ribonucleoprotein complex compositions, impacting their functions.
Area of Science:
- Molecular Biology
- Virology
- Genetics
Background:
- Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3F (APOBEC3F) and A3G are key antiviral proteins.
- These proteins share significant sequence identity and inhibit retroelements.
Purpose of the Study:
- To comparatively analyze the protein and RNA composition of APOBEC3F (A3F) and A3G-associated ribonucleoprotein complexes (RNPs).
- To understand the structural basis for potential functional differences between A3F and A3G.
Main Methods:
- Comparative analysis of protein and RNA components within A3F and A3G RNPs.
- Assessment of RNP association with cytoplasmic microdomains (processing bodies, stress granules).
- Evaluation of RNP resistance to RNase digestion and identification of associated RNAs.
Main Results:
- Both A3F and A3G associate with cytoplasmic RNPs and accumulate in processing bodies and stress granules.
- A3F RNPs show greater resistance to RNase digestion compared to A3G RNPs.
- A3F RNPs lack Ro60, La autoantigens, Y RNAs, and 7SL RNA, but contain Alu RNA, similar to A3G RNPs.
Conclusions:
- Subtle differences exist in the protein and RNA composition of A3F and A3G RNPs.
- These compositional differences likely contribute to the distinct functional properties of A3F and A3G in retroelement restriction.
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