Cellular inhibitors of long interspersed element 1 and Alu retrotransposition.
Long interspersed element (LINE) 1 retrotransposons are major genomic parasites that represent approximately 17% of the human genome. The LINE-1 ORF2 protein is also responsible for the mobility of Alu elements, which constitute a further approximately 11% of genomic DNA. Representative members of each element class remain mobile, and deleterious retrotransposition events can induce spontaneous genetic diseases. Here, we demonstrate that APOBEC3A and APOBEC3B, two members of the APOBEC3 family of human innate antiretroviral resistance factors, can enter the nucleus, where LINE-1 and Alu reverse transcription occurs, and specifically inhibit both LINE-1 and Alu retrotransposition. These data suggest that the APOBEC3 protein family may have evolved, at least in part, to defend the integrity of the human genome against endogenous retrotransposons.
Bogerd
Hal P
HP
Center for Virology and Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
Wiegand
Heather L
HL
Hulme
Amy E
AE
Garcia-Perez
José L
JL
O'Shea
K Sue
KS
Moran
John V
JV
Cullen
Bryan R
BR
D000071478:APOBEC Deaminases; D020087:Alu Elements / Q000235:genetics*; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase / Q000235:genetics; D004251:DNA Transposable Elements / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D006367:HeLa Cells; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D004251:DNA Transposable Elements; D012333:RNA, Messenger; D043525:Cytosine Deaminase; D000071478:APOBEC Deaminases; C502889:APOBEC3 proteins, human; D003564:Cytidine Deaminase