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Influenza virus natural sequence heterogeneity in segment 8 affects interactions with cellular RNA-binding proteins and splicing efficiency

Nilsson, Kersti LU ; Abdurahman, Samir and Schwartz, Stefan LU (2020) In Virology 549. p.39-50
Abstract

Segment 8 mRNAs of influenza virus A/Brevig Misson/1918/1 (H1N1) are poorly spliced compared to segment 8 mRNAs of influenza virus A/Netherlands/178/95 (H3N2). Using oligonucleotide-mediated protein pull down with oligos spanning the entire length of segment 8 of either influenza virus H1N1 or influenza virus H3N2 we identified cellular RNA binding proteins that interacted with oligonucleotides derived from either H1N1 or H3N2 sequences. When the identified hot spots for RNA binding proteins in H1N1 segment 8 mRNAs were replaced by H3N2 sequences, splicing efficiency increased significantly. Replacing as few as three nucleotides of the H1N1 mRNA with sequences from H3N2 mRNA, enhanced splicing of the H1N1 mRNAs. Cellular proteins U2AF65... (More)

Segment 8 mRNAs of influenza virus A/Brevig Misson/1918/1 (H1N1) are poorly spliced compared to segment 8 mRNAs of influenza virus A/Netherlands/178/95 (H3N2). Using oligonucleotide-mediated protein pull down with oligos spanning the entire length of segment 8 of either influenza virus H1N1 or influenza virus H3N2 we identified cellular RNA binding proteins that interacted with oligonucleotides derived from either H1N1 or H3N2 sequences. When the identified hot spots for RNA binding proteins in H1N1 segment 8 mRNAs were replaced by H3N2 sequences, splicing efficiency increased significantly. Replacing as few as three nucleotides of the H1N1 mRNA with sequences from H3N2 mRNA, enhanced splicing of the H1N1 mRNAs. Cellular proteins U2AF65 and HuR interacted preferentially with the 3′-splice site of H3N2 and overexpression of HuR reduced the levels of unspliced H1N1 mRNAs, suggesting that U2AF65 and HuR contribute to control of influenza virus mRNA splicing.

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author
; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
hnRNP, HuR, Influenza, Spanish flu, Splicing, SR-Protein, U2AF65
in
Virology
volume
549
pages
12 pages
publisher
Elsevier
external identifiers
  • pmid:32829114
  • scopus:85089481626
ISSN
0042-6822
DOI
10.1016/j.virol.2020.08.005
language
English
LU publication?
yes
id
cf87a86e-91d6-4ed9-a0bd-cedc1ebd8bda
date added to LUP
2020-08-27 10:20:47
date last changed
2024-09-19 06:25:04
@article{cf87a86e-91d6-4ed9-a0bd-cedc1ebd8bda,
  abstract     = {{<p>Segment 8 mRNAs of influenza virus A/Brevig Misson/1918/1 (H1N1) are poorly spliced compared to segment 8 mRNAs of influenza virus A/Netherlands/178/95 (H3N2). Using oligonucleotide-mediated protein pull down with oligos spanning the entire length of segment 8 of either influenza virus H1N1 or influenza virus H3N2 we identified cellular RNA binding proteins that interacted with oligonucleotides derived from either H1N1 or H3N2 sequences. When the identified hot spots for RNA binding proteins in H1N1 segment 8 mRNAs were replaced by H3N2 sequences, splicing efficiency increased significantly. Replacing as few as three nucleotides of the H1N1 mRNA with sequences from H3N2 mRNA, enhanced splicing of the H1N1 mRNAs. Cellular proteins U2AF65 and HuR interacted preferentially with the 3′-splice site of H3N2 and overexpression of HuR reduced the levels of unspliced H1N1 mRNAs, suggesting that U2AF65 and HuR contribute to control of influenza virus mRNA splicing.</p>}},
  author       = {{Nilsson, Kersti and Abdurahman, Samir and Schwartz, Stefan}},
  issn         = {{0042-6822}},
  keywords     = {{hnRNP; HuR; Influenza; Spanish flu; Splicing; SR-Protein; U2AF65}},
  language     = {{eng}},
  pages        = {{39--50}},
  publisher    = {{Elsevier}},
  series       = {{Virology}},
  title        = {{Influenza virus natural sequence heterogeneity in segment 8 affects interactions with cellular RNA-binding proteins and splicing efficiency}},
  url          = {{http://dx.doi.org/10.1016/j.virol.2020.08.005}},
  doi          = {{10.1016/j.virol.2020.08.005}},
  volume       = {{549}},
  year         = {{2020}},
}