tetano
Editor, Senior Moderator
Nat Commun. 2018 Jun 19;9(1):2407. doi: 10.1038/s41467-018-04779-4.
[h=1]Co-regulatory activity of hnRNP K and NS1-BP in influenza and human mRNA splicing.[/h] Thompson MG[SUP]1[/SUP], Mu?oz-Moreno R[SUP]2,[/SUP][SUP]3[/SUP], Bhat P[SUP]4[/SUP], Roytenberg R[SUP]1[/SUP], Lindberg J[SUP]1[/SUP], Gazzara MR[SUP]1[/SUP], Mallory MJ[SUP]1[/SUP], Zhang K[SUP]4[/SUP], Garc?a-Sastre A[SUP]2,[/SUP][SUP]3,[/SUP][SUP]5[/SUP], Fontoura BMA[SUP]4[/SUP], Lynch KW[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Three of the eight RNA segments encoded by the influenza A virus (IAV) undergo alternative splicing to generate distinct proteins. Previously, we found that host proteins hnRNP K and NS1-BP regulate IAV M segment splicing, but the mechanistic details were unknown. Here we show NS1-BP and hnRNP K bind M mRNA downstream of the M2 5' splice site (5'ss). NS1-BP binds most proximal to the 5'ss, partially overlapping the U1 snRNP binding site, while hnRNP K binds further downstream and promotes U1 snRNP recruitment. Mutation of either or both the hnRNP K and NS1-BP-binding sites results in M segment mis-splicing and attenuated IAV replication. Additionally, we show that hnRNP K and NS1-BP regulate host splicing events and that viral infection causes mis-splicing of some of these transcripts. Therefore, our proposed mechanism of hnRNP K/NS1-BP mediated IAV M splicing provides potential targets of antiviral intervention and reveals novel host functions for these proteins.
PMID: 29921878 PMCID: PMC6008300 DOI: 10.1038/s41467-018-04779-4
[h=1]Co-regulatory activity of hnRNP K and NS1-BP in influenza and human mRNA splicing.[/h] Thompson MG[SUP]1[/SUP], Mu?oz-Moreno R[SUP]2,[/SUP][SUP]3[/SUP], Bhat P[SUP]4[/SUP], Roytenberg R[SUP]1[/SUP], Lindberg J[SUP]1[/SUP], Gazzara MR[SUP]1[/SUP], Mallory MJ[SUP]1[/SUP], Zhang K[SUP]4[/SUP], Garc?a-Sastre A[SUP]2,[/SUP][SUP]3,[/SUP][SUP]5[/SUP], Fontoura BMA[SUP]4[/SUP], Lynch KW[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Three of the eight RNA segments encoded by the influenza A virus (IAV) undergo alternative splicing to generate distinct proteins. Previously, we found that host proteins hnRNP K and NS1-BP regulate IAV M segment splicing, but the mechanistic details were unknown. Here we show NS1-BP and hnRNP K bind M mRNA downstream of the M2 5' splice site (5'ss). NS1-BP binds most proximal to the 5'ss, partially overlapping the U1 snRNP binding site, while hnRNP K binds further downstream and promotes U1 snRNP recruitment. Mutation of either or both the hnRNP K and NS1-BP-binding sites results in M segment mis-splicing and attenuated IAV replication. Additionally, we show that hnRNP K and NS1-BP regulate host splicing events and that viral infection causes mis-splicing of some of these transcripts. Therefore, our proposed mechanism of hnRNP K/NS1-BP mediated IAV M splicing provides potential targets of antiviral intervention and reveals novel host functions for these proteins.
PMID: 29921878 PMCID: PMC6008300 DOI: 10.1038/s41467-018-04779-4