High-molecular-mass APOBEC3G complexes restrict Alu retrotransposition.

Area of Science:

• Molecular Biology
• Virology
• Genetics

Background:

• APOBEC3G (A3G) is an intrinsic antiretroviral factor with two forms: enzymatically active low-molecular-mass (LMM) and inactive high-molecular-mass (HMM) ribonucleoprotein complex.
• Resting CD4 T cells express LMM A3G, a restriction factor against HIV-1.
• Activated CD4 T cells recruit LMM A3G into HMM complexes of unknown function.

Purpose of the Study:

• To elucidate the function of high-molecular-mass (HMM) APOBEC3G (A3G) complexes.
• To identify the cellular targets and mechanisms of HMM A3G.
• To understand the dual role of A3G in combating exogenous retroviruses and endogenous retroelements.

Main Methods:

• Tandem affinity purification coupled with mass spectrometry (MS) to identify HMM A3G complex components.
• RNA analysis to determine RNAs recruited into HMM A3G complexes.
• Assays to evaluate the inhibition of retrotransposition of marked Alu retroelements.

Main Results:

• HMM A3G complexes contain Staufen-containing RNA-transporting granules and Ro ribonucleoprotein complexes.
• Alu and small Y RNAs, nonautonomous mobile genetic elements, are recruited into HMM A3G complexes.
• A3G inhibits L1-dependent Alu retrotransposition by sequestering Alu RNAs in cytoplasmic HMM A3G complexes, not by inhibiting L1 function.

Conclusions:

• Nonautonomous Alu and Y RNAs are natural cellular targets of A3G.
• LMM A3G protects against exogenous retroviruses like HIV-1.
• HMM A3G protects against endogenous retroelements by sequestering their RNA components.