Paramyxovirus mRNA editing leads to G deletions as well as insertions.
Paramyxoviruses are thought to edit their P gene mRNAs co-transcriptionally, by a mechanism in which the polymerase stutters and reads the same template base more than once. Sendai virus (SeV) and bovine parainfluenza virus type 3 (bPIV3) are closely related viruses, but SeV edits its P gene mRNA with the insertion of a single G residue (at approximately 50% frequency) within the sequence 5' A6G3, whereas bPIV3 inserts 1 to approximately 6 Gs at roughly equal frequency within the sequence 5' A6G4. When SeV synthetic mini-genomes containing either SeV or bPIV3 P gene editing cassettes are expressed from cDNA in cells which are also transfected with the SeV NP, P and L genes, the virus-specific editing patterns were reproduced. Since the bPIV3 editing pattern was reproduced in a system that is otherwise completely SeV, this suggests that all the information for the virus-specific editing patterns is due to the RNA sequence itself. Unexpectedly, the length of the template C run was found to be critical, even though it varies from 3 to 7 nucleotides in length in different viruses. Expanding this template C run first led to attenuation of the insertion phenotype, and then to deletions rather than insertions. A stuttering or slippage model to account for these events has been further refined to include a pressure which displaces the nascent strand in a given direction once it has disengaged from the template, and the similarities of this model to those which account for readthrough of cellular RNA polymerase transcription blocks are discussed.
Jacques
J P
JP
Department of Genetics and Microbiology, University of Geneva School of Medicine, Switzerland.
Hausmann
S
S
Kolakofsky
D
D
D001483:Base Sequence; D018076:DNA, Complementary / Q000235:genetics; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral; D005822:Genetic Vectors; D006147:Guanine; D006367:HeLa Cells; D006801:Humans; D008957:Models, Genetic; D008969:Molecular Sequence Data; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D010222:Parainfluenza Virus 1, Human / Q000235:genetics*; D010641:Phenotype; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics*; D017354:Point Mutation; D012333:RNA, Messenger / Q000235:genetics*; D012367:RNA, Viral / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D017384:Sequence Deletion; D013698:Templates, Genetic; D014162:Transfection; D014758:Viral Core Proteins / Q000096:biosynthesis / Q000235:genetics*; D014764:Viral Proteins / Q000096:biosynthesis / Q000235:genetics*; D015678:Viral Structural Proteins / Q000235:genetics*
D018076:DNA, Complementary; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; C055859:P protein, Sendai virus; D010750:Phosphoproteins; D012333:RNA, Messenger; D012367:RNA, Viral; D011993:Recombinant Fusion Proteins; D014758:Viral Core Proteins; D014764:Viral Proteins; D015678:Viral Structural Proteins; D006147:Guanine; C062210:bacteriophage T7 RNA polymerase; C064365:L protein, Sendai virus; D012321:DNA-Directed RNA Polymerases