Interaction of Staufen1 with the 5' end of mRNA facilitates translation of these RNAs

Abstract

Staufen1 is a component of transported ribonucleoprotein complexes. Genetic work in Drosophila has suggested that Staufen plays a role in the de-repression of translation of oskar mRNA following localization. To determine whether Staufen1 can play a similar role in mammals, we studied translation of transcripts in the presence or in the absence of Staufen1. Translationally repressed mRNAs were generated by fusing the structured human immunodeficiency virus type 1 trans-activating response (TAR) element to the 5′ end of a reporter transcript. In rabbit reticulocyte lysates and in mammalian cultured cells, the addition of Staufen1 resulted in the up-regulation of reporter activity when translation was driven by the TAR-bearing RNA. In contrast, Staufen1 had no effect on translation of efficiently translated mRNAs lacking an apparent structured 5′ end, suggesting that Staufen1-binding to the 5′ end is required for enhanced translation. Consistently, Staufen1 RNA-binding activity is necessary for this translational effect. In addition, similar up-regulation of translation was observed when Staufen1 was tethered to the 5′ end of mRNAs via other structured RNAs, the highest level of translational increase being obtained with the bona fide Staufen1-binding site of the Arf1 transcript. The expression of Staufen1 promoted polysomal loading of TAR-luciferase transcripts resulting in enhanced translation. Our results support a model in which the expression of Staufen1 and its interaction with the 5′ end of RNA and ribosomes facilitate translation initiation.

Genome wide identification of Staufen2-bound mRNAs in embryonic rat brains

“…Alternatively, based on known functions of its paralog Stau1, Stau2 may also control the stability or the translation of specific mRNAs. Indeed, Stau1 elicits mRNA decay of a sub-population of transcripts when bound to their 3'UTR (21) and enhances translation of other mRNAs when bound to their 5'UTR (22). This latter function of Stau1 is consistent with a role of Drosophila Staufen in oskar mRNA translation once localized to the posterior pole (23,24).…”

Staufen1 senses overall transcript secondary structure to regulate translation

“…Which activity is observed depends on the cellular context, the identity of the bound RNA and the location of the binding site on the target RNA. Many of Staufen's previously documented activities parallel those of the EJC [7][8][9][10][11]19,20,33,[35][36][37][38] . To better understand EJC function, we recently determined the complete EJC RNA-binding landscape in HEK293 cells 24 .…”

“…In flies, 3′ UTR-bound Staufen is required for proper localization and translational control of bicoid and prospero mRNAs during oogenesis 4,5 . In mammals, Stau1 has been implicated in mRNA transport to neuronal dendrites 6 , regulation of translation via physical interaction with the ribosome 7 , a form of translation-dependent mRNA degradation known as Staufen-mediated decay (SMD) [8][9][10][11] , regulation of stress-granule homeostasis 12 , alternative splicing, nuclear export and translation of a gene containing 3′-UTR CUG-repeat expansions 13 . Although Stau1 is not essential for mammalian development, neurons lacking Stau1 have dendritic spinemorphogenesis defects in vitro, and knockout mice have locomotor-activity deficits 14 .…”

The Anti-HIV-1 Editing Enzyme APOBEC3G Binds HIV-1 RNA and Messenger RNAs That Shuttle between Polysomes and Stress Granules

“…For example, Stau1 helps to localize some actively translated mRNAs at specific subcellular sites (56 -58, 69), and it occurs together with Upf1 on specific polysomal mRNAs (57). It also binds to the HIV-1 TAR sequence and stimulates translation of HIV-1 RNA and other RNAs that have double-stranded hairpin regions (56). Our analyses are consistent with this expected broad functional and subcellular distribution of Stau1, which only partially overlaps with the subcellular distribution of A3G (Figs.…”

“…Stau1 to the Gag precursor (65)) or HIV-1 RNA (e.g. PABP1 binds to a region in the Gag coding sequence and controls Gag expression (70), whereas Pur␣, YB-1, and Stau1 bind to the TAR sequence (56,(71)(72)(73)). Other proteins of potential interest include hnRNP Q that associates with APOBEC1 (74) and interleukin-binding proteins 2 and 3 (NF45 and NF90, respectively), which are essential for encapsidation and protein priming of hepatitis B viral polymerase (75).…”