STAU1 binding 3′ UTR IRAlus complements nuclear retention to protect cells from PKR-mediated translational shutdown

For a number of human genes that encode transcripts containing inverted repeat Alu elements (IRAlus) within their 3′ untranslated region (UTR), product mRNA is efficiently exported to the cytoplasm when the IRAlus, which mediate nuclear retention, are removed by alternative polyadenylation. Here we report a new mechanism that promotes gene expression by targeting mRNAs that maintain their 3′ UTR IRAlus: Binding of the dsRNA-binding protein Staufen1 (STAU1) to 3′ UTR IRAlus inhibits nuclear retention so as to augment the nuclear export of 3′ UTR IRAlus-containing mRNAs (IRAlus mRNAs). Moreover, we found that 3′ UTR IRAlus-bound STAU1 enhances 3′ UTR IRAlus mRNA translation by precluding protein kinase R (PKR) binding, which obviates PKR activation, eukaryotic translation initiation factor 2α (eIF2α) phosphorylation, and repression of global cell translation. Thus, STAU1 binding to 3′ UTR IRAlus functions along with 3′ UTR IRAlus-mediated nuclear retention to suppress the shutdown of cellular translation triggered by PKR binding to endogenous cytoplasmic dsRNAs. We also show that a changing STAU1/PKR ratio contributes to myogenesis via effects on the 3′ UTR IRAlus of mRNA encoding the microRNA-binding protein LIN28.

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