title: RNA editing and alternative splicing of the insect nAChR subunit alpha6 transcript: evolutionary conservation, divergence and regulation.
abstract: BACKGROUND
  RNA editing and alternative splicing play an important role in expanding protein diversity and this is well illustrated in studies of nicotinic acetylcholine receptors (nAChRs).
  
  
  RESULTS
  Here, we compare the RNA editing and alternative splicing of the nAChR alpha6 subunit genes from different insects spanning ~300 million years of evolution- Drosophila melanogaster, Anopheles gambiae, Bombyx mori, Tribolium castaneum and Apis mellifera. The conserved and species-specific A-to-I RNA editing occurred across all species except A. gambiae, which displayed extraordinarily short flanking intronic sequences. Interestingly, some A-to-I editing sites were a genomically encoded G in other species. A combination of the experimental data and computational analysis of orthologous alpha6 genes from different species indicated that RNA editing and alternative splicing predated at least the radiation of insect orders spanning ~300 million years of evolution; however, they might have been lost in some species during subsequent evolution. The occurrence of alternative splicing was found to be regulated in distinct modes and, in some cases, even correlated with RNA editing.
  
  
  CONCLUSIONS
  On the basis of comparative analysis of orthologous nAChR alpha6 genes from different insects spanning ~300 million years of evolution, we have documented the existence, evolutionary conservation and divergence, and also regulation of RNA editing and alternative splicing. Phylogenetic analysis of RNA editing and alternative splicing, which can create a multitude of functionally distinct protein isoforms, might have a crucial role in the evolution of complex organisms beyond nucleotide and protein sequences.
authors.affiliation: Institute of Biochemistry, College of Life Sciences, Zhejiang University (Zijingang Campus), Hangzhou, Zhejiang, PR of China. jinyf@zju.edu.cn
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Jin
authors.forename: Nan
authors.initials: N
authors.lastname: Tian
authors.forename: Jun
authors.initials: J
authors.lastname: Cao
authors.forename: Jing
authors.initials: J
authors.lastname: Liang
authors.forename: Zhaolin
authors.initials: Z
authors.lastname: Yang
authors.forename: Jianning
authors.initials: J
authors.lastname: Lv
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D000852:Anopheles / Q000235:genetics; D001483:Base Sequence; D001516:Bees / Q000235:genetics; D012831:Bombyx / Q000196:embryology / Q000235:genetics / Q000254:growth & development; D017124:Conserved Sequence; D018076:DNA, Complementary / Q000235:genetics; D004330:Drosophila / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics; D004331:Drosophila melanogaster / Q000235:genetics; D019143:Evolution, Molecular; D005091:Exons / Q000235:genetics; D017344:Genes, Insect; D019476:Insect Proteins / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D017393:RNA Editing; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017385:Sequence Homology; D013045:Species Specificity; D014231:Tribolium / Q000235:genetics
chemical_list: D018076:DNA, Complementary; D029721:Drosophila Proteins; D019476:Insect Proteins; D011978:Receptors, Nicotinic; C113681:nicotinic acetylcholine receptor alpha-subunits, Drosophila; C104518:nicotinic receptor alpha6