Abstract |
Mouse apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like editing complex 3 (mA3), an intracellular antiviral factor, has 2 allelic variations that are linked with different susceptibilities to beta- and gammaretrovirus infections among various mouse strains. In virus-resistant C57BL/6 (B6) mice, mA3 transcripts are more abundant than those in susceptible BALB/c mice both in the spleen and bone marrow. These strains of mice also express mA3 transcripts with different splicing patterns: B6 mice preferentially express exon 5-deficient (Δ5) mA3 mRNA, while BALB/c mice produce exon 5-containing full-length mA3 mRNA as the major transcript. Although the protein product of the Δ5 mRNA exerts stronger antiretroviral activities than the full-length protein, how exon 5 affects mA3 antiviral activity, as well as the genetic mechanisms regulating exon 5 inclusion into the mA3 transcripts, remains largely uncharacterized. Here we show that mA3 exon 5 is indeed a functional element that influences protein synthesis at a post-transcriptional level. We further employed in vitro splicing assays using genomic DNA clones to identify two critical polymorphisms affecting the inclusion of exon 5 into mA3 transcripts: the number of TCCT repeats upstream of exon 5 and the single nucleotide polymorphism within exon 5 located 12 bases upstream of the exon 5/intron 5 boundary. Distribution of the above polymorphisms among different Mus species indicates that the inclusion of exon 5 into mA3 mRNA is a relatively recent event in the evolution of mice. The widespread geographic distribution of this exon 5-including genetic variant suggests that in some Mus populations the cost of maintaining an effective but mutagenic enzyme may outweigh its antiviral function.
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Authors | Jun Li, Yoshiyuki Hakata, Eri Takeda, Qingping Liu, Yasumasa Iwatani, Christine A Kozak, Masaaki Miyazawa |
Journal | PLoS pathogens
(PLoS Pathog)
Vol. 8
Issue 1
Pg. e1002478
(Jan 2012)
ISSN: 1553-7374 [Electronic] United States |
PMID | 22275865
(Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- RNA, Messenger
- Regulatory Sequences, Ribonucleic Acid
- Apobec3 protein, mouse
- Cytidine Deaminase
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Topics |
- Animals
- Biological Evolution
- Cell Line, Transformed
- Cytidine Deaminase
(genetics, metabolism)
- Exons
- Mice
- Mice, Inbred BALB C
- Mice, Inbred C57BL
- Mice, Knockout
- Mutagenesis, Site-Directed
- Polymorphism, Single Nucleotide
(genetics)
- Protein Biosynthesis
(genetics)
- Protein Stability
- RNA Splicing
(genetics)
- RNA, Messenger
(chemistry, genetics)
- Regulatory Sequences, Ribonucleic Acid
(genetics)
- Retroviridae
(physiology)
- Retroviridae Infections
(virology)
- Sequence Deletion
- Species Specificity
- Tumor Virus Infections
(virology)
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