Paramyxovirus mRNA editing leads to G deletions as well as insertions

EMBO J. 1994 Nov 15;13(22):5496-503.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • DNA, Complementary / genetics
  • DNA-Directed RNA Polymerases / metabolism
  • Gene Expression Regulation, Viral*
  • Genes, Viral*
  • Genetic Vectors
  • Guanine
  • HeLa Cells
  • Humans
  • Models, Genetic*
  • Molecular Sequence Data
  • Nucleocapsid Proteins
  • Nucleoproteins*
  • Parainfluenza Virus 1, Human / genetics*
  • Phenotype
  • Phosphoproteins / biosynthesis
  • Phosphoproteins / genetics*
  • Point Mutation*
  • RNA, Messenger / genetics*
  • RNA, Viral / genetics*
  • Recombinant Fusion Proteins / biosynthesis
  • Sequence Deletion*
  • Templates, Genetic
  • Transfection
  • Viral Core Proteins / biosynthesis
  • Viral Core Proteins / genetics*
  • Viral Proteins / biosynthesis
  • Viral Proteins / genetics*
  • Viral Structural Proteins / genetics*

Substances

  • DNA, Complementary
  • Nucleocapsid Proteins
  • Nucleoproteins
  • P protein, Sendai virus
  • Phosphoproteins
  • RNA, Messenger
  • RNA, Viral
  • Recombinant Fusion Proteins
  • Viral Core Proteins
  • Viral Proteins
  • Viral Structural Proteins
  • Guanine
  • bacteriophage T7 RNA polymerase
  • L protein, Sendai virus
  • DNA-Directed RNA Polymerases