Sequences of mRNAs derived from genome RNA segment 7 of influenza virus: colinear and interrupted mRNAs code for overlapping proteins.

Lamb, Robert A.; Lai, Ching-Juh; Choppin, Purnell W.

doi:10.1073/pnas.78.7.4170

Cited by 281 publications

(217 citation statements)

References 32 publications

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“…M1 mRNA is colinear with the viral RNA, while M2 mRNA is encoded by a spliced transcript (29,52). The proteins encoded by these mRNAs share their initial 9 amino acids and also have a stretch of 14 amino acids in overlapping reading frames.…”

mentioning

confidence: 99%

Characterization of the 1918 “Spanish” Influenza Virus Matrix Gene Segment

Reid

Fanning

Janczewski

et al. 2002

J Virol

101

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The coding region of influenza A virus RNA segment 7 from the 1918 pandemic virus, consisting of the open reading frames of the two matrix genes M1 and M2, has been sequenced. While this segment is highly conserved among influenza virus strains, the 1918 sequence does not match any previously sequenced influenza virus strains. The 1918 sequence matches the consensus over the M1 RNA-binding domains and nuclear localization signal and the highly conserved transmembrane domain of M2. Amino acid changes that correlate with high yield and pathogenicity in animal models were not found in the 1918 strain. Phylogenetic analyses suggest that both genes were mammalian adapted and that the 1918 sequence is very similar to the common ancestor of all subsequent human and classical swine matrix segments. The 1918 sequence matches other mammalian strains at 4 amino acids in the extracellular domain of M2 that differ consistently between avian and mammalian strains, suggesting that the matrix segment may have been circulating in human strains for at least several years before 1918.

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mentioning

confidence: 99%

Characterization of the 1918 “Spanish” Influenza Virus Matrix Gene Segment

Reid

Fanning

Janczewski

et al. 2002

J Virol

101

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“…5). This indicates that the RNPs containing The affinity-purified 55S complexes formed with biotinythese snRNAs were specifically associated with NS1 mRNA 20 4. Kinetics of 55S complex formation with NS1 mRNA and the adenovirus (AD) pKT1 transcript using splicing fractions II plus Ib.…”

Section: Methodsmentioning

confidence: 99%

“…Because both the unspliced (NS1 and Ml) and spliced (NS2 and M2) mRNAs code for proteins, the extent of splicing is regulated. In influenza virus-infected cells, this regulation results in a steady-state amount of the spliced mRNAs that is only about 10% of that of the unspliced mRNAs (17,20). This type of splicing regulation is not restricted to influenza virus.…”

mentioning

confidence: 99%

“…Two influenza virus mRNAs, the NS1 and Ml mRNAs, are spliced in the nucleus to form two smaller mRNAs, NS2 and M2, respectively (12,18,20). Of the pre-mRNAs that undergo splicing, the influenza virus NS1 and Ml mRNAs are the only known examples that are not DNA directed and that are not synthesized by RNA polymerase II.…”

mentioning

confidence: 99%

“…The association of the Ul snRNPs with the 50S to 60S spliceosomes appears to be more labile than that of the other snRNPs (2,11,33 interact with the 5' splice site and intron branch point, respectively. The 50S to 60S spliceosomes contain the products of the first step in splicing, 5' exon and lariat-3' exon, indicating that these spliceosomes are functional structures (1,4,7,10,24).Two influenza virus mRNAs, the NS1 and Ml mRNAs, are spliced in the nucleus to form two smaller mRNAs, NS2 and M2, respectively (12,18,20). Of the pre-mRNAs that undergo splicing, the influenza virus NS1 and Ml mRNAs are the only known examples that are not DNA directed and that are not synthesized by RNA polymerase II.…”

mentioning

confidence: 99%

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A block in mammalian splicing occurring after formation of large complexes containing U1, U2, U4, U5, and U6 small nuclear ribonucleoproteins.

Agris¹,

Nemeroff²,

Krug³

1989

Mol. Cell. Biol.

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The assembly of mammalian pre-mRNAs into large 50S to 60S complexes, or spliceosomes, containing small nuclear ribonucleoproteins (snRNPs) leads to the production of splicing intermediates, 5' exon and lariat-3' exon, and the subsequent production of spliced products. Influenza virus NS1 mRNA, which encodes a virus-specific protein, is spliced in infected cells to form another viral mRNA (the NS2 mRNA), such that the ratio of unspliced to spliced mRNA is 10 to 1. NS1 mRNA was not detectably spliced in vitro with nuclear extracts from uninfected HeLa cells. Surprisingly, despite the almost total absence of splicing intermediates in the in vitro reaction, NS1 mRNA very efficiently formed ATP-dependent 55S complexes. The formation of 55S complexes with NS1 mRNA was compared with that obtained with an adenovirus pre-mRNA (pKT1 transcript) by using partially purified splicing fractions that restricted the splicing of the pKT1 transcript to the production of splicing intermediates. At RNA precursor levels that were considerably below saturation, approximately 10-fold more of the input NS1 mRNA than of the input pKT1 transcript formed 55S complexes at all time points examined. The pKT1 55S complexes contained splicing intermediates, whereas the NS1 55S complexes contained only precursor NS1 mRNA. Biotin-avidin affinity chromatography showed that the 55S complexes formed with either NS1 mRNA or the pKT1 transcript contained the Ul, U2, U4, U5, and U6 snRNPs. Consequently, the formation of 55S complexes containing these five snRNPs was not sufficient for the catalysis of the first step of splicing, indicating that some additional step(s) needs to occur subsequent to this binding. These results indicate that the 5' splice site, 3' splice site, and branchpoint of NS1 mRNA were capable of interacting with the five snRNPs to form 55S complexes, but apparently some other sequence element(s) in NS1 mRNA blocked the resolution of the 55S complexes that leads to the catalysis of splicing. On the basis of our results, we suggest mechanisms by which the splicing of NS1 mRNA is controlled in infected cells.Eucaryotic pre-mRNAs synthesized by RNA polymerase II usually contain intervening sequences (introns) that are removed by splicing. The first step is cleavage at the 5' splice site, to generate the 5' exon and a lariat form of the intron attached to the 3' exon. Subsequently, the 5' and 3' exons are ligated to form the mature mRNA and to release the intron lariat (23,27). During the initial phase of the reaction, the pre-mRNA substrate is assembled into ribonucleoprotein complexes, or spliceosomes, containing small nuclear ribonucleoproteins (snRNPs) (1,4,7,10,24). The largest complexes found in mammalian systems sediment at about 50S to 60S in sucrose gradients (1,7,10,24). Analysis of the snRNP composition of 50S to 60S spliceosomes by affinity selection of biotinylated pre-mRNA on streptavidin-agarose beads indicated that the Ul, U2, U4, U5, and U6 snRNPs are present in these spliceosomes (2, 11). The same snRNPs have been ide...

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