A genome-wide RNAi screen reveals that mRNA decapping restricts bunyaviral replication by limiting the pools of Dcp2-accessible targets for cap-snatching

Bunyaviruses are an emerging group of medically important viruses, many of which are transmitted from insects to mammals. To identify host factors that impact infection, we performed a genome-wide RNAi screen in Drosophila and identified 131 genes that impacted infection of the mosquito-transmitted bunyavirus Rift Valley fever virus (RVFV). Dcp2, the catalytic component of the mRNA decapping machinery, and two decapping activators, DDX6 and LSM7, were antiviral against disparate bunyaviruses in both insect cells and adult flies. Bunyaviruses 5′ cap their mRNAs by “cap-snatching” the 5′ ends of poorly defined host mRNAs. We found that RVFV cap-snatches the 5′ ends of Dcp2 targeted mRNAs, including cell cycle-related genes. Loss of Dcp2 allows increased viral transcription without impacting viral mRNA stability, while ectopic expression of Dcp2 impedes viral transcription. Furthermore, arresting cells in late S/early G2 led to increased Dcp2 mRNA targets and increased RVFV replication. Therefore, RVFV competes for the Dcp2-accessible mRNA pool, which is dynamically regulated and can present a bottleneck for viral replication.

KEYWORDS

SHARE & LIKE

COMMENTS

ABOUT THE AUTHOR

基因与发育(GENES & DEVELOPMENT)

0 Following 0 Fans 0 Projects 8 Articles

SIMILAR ARTICLES

The R-spondin (RSPO) family of secreted proteins (RSPO1–RSPO4) has pleiotropic functions in development and stem cell growth by strongly enhancing Wnt

Read More

Regulated gene expression determines the intrinsic ability of neurons to extend axons, and loss of such ability is the major reason for the failed axon

Read More

In mammals, homologs that fail to synapse during meiosis are transcriptionally inactivated. This process, meiotic silencing, drives inactivation of the

Read More

For a number of human genes that encode transcripts containing inverted repeat Alu elements (IRAlus) within their 3′ untranslated region (UTR), product

Read More

Bunyaviruses are an emerging group of medically important viruses, many of which are transmitted from insects to mammals. To identify host factors that

Read More

The mammalian circadian timing system consists of a master pacemaker in the suprachiasmatic nucleus (SCN) in the hypothalamus, which is thought to set

Read More

Macroautophagy (autophagy hereafter) degrades and recycles proteins and organelles to support metabolism and survival in starvation. Oncogenic Ras up-r

Read More

With the advent of high-throughput sequencing technologies, much progress has been made in the identification of somatic structural rearrangements in c

Read More