Human L1 retrotransposition: cis preference versus trans complementation.
Long interspersed nuclear elements (LINEs or L1s) comprise approximately 17% of human DNA; however, only about 60 of the approximately 400,000 L1s are mobile. Using a retrotransposition assay in cultured human cells, we demonstrate that L1-encoded proteins predominantly mobilize the RNA that encodes them. At much lower levels, L1-encoded proteins can act in trans to promote retrotransposition of mutant L1s and other cellular mRNAs, creating processed pseudogenes. Mutant L1 RNAs are mobilized at 0.2 to 0.9% of the retrotransposition frequency of wild-type L1s, whereas cellular RNAs are mobilized at much lower frequencies (ca. 0.01 to 0.05% of wild-type levels). Thus, we conclude that L1-encoded proteins demonstrate a profound cis preference for their encoding RNA. This mechanism could enable L1 to remain retrotransposition competent in the presence of the overwhelming number of nonfunctional L1s present in human DNA.
Wei
W
W
Department of Human Genetics, The University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Gilbert
N
N
Ooi
S L
SL
Lawler
J F
JF
Ostertag
E M
EM
Kazazian
H H
HH
Boeke
J D
JD
Moran
J V
JV
D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D019143:Evolution, Molecular; D005816:Genetic Complementation Test; D006367:HeLa Cells; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D008957:Models, Genetic; D009154:Mutation; D016366:Open Reading Frames; D011544:Pseudogenes; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic
D017931:DNA Primers; D012333:RNA, Messenger