Co-regulatory Activity of HnRNP K and NS1-BP in Influenza and Human MRNA Splicing

Overview

Journal Nat Commun

Specialty Biology

Date 2018 Jun 21

PMID 29921878

Citations 40

Authors

Matthew G Thompson

Raquel Munoz-Moreno

Prasanna Bhat

Renat Roytenberg

John Lindberg

Matthew R Gazzara

Michael J Mallory

Ke Zhang

Adolfo Garcia-Sastre

Beatriz M A Fontoura

Kristen W Lynch

Affiliations

Soon will be listed here.

Abstract

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.

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