Dendritic localization and hence local mRNA translation contributes to synaptic plasticity in neurons. Staufen2 (Stau2) is a well-known neuronal double-stranded RNA-binding protein (dsRBP) that has been implicated in dendritic mRNA localization. The specificity of Stau2 binding to its target mRNAs remains elusive. Using individual-nucleotide resolution CLIP (iCLIP), we identified significantly enriched Stau2 binding to the 3'-UTRs of 356 transcripts. In 28 (7.9%) of those, binding occurred to a retained intron in their 3'-UTR The strongest bound 3'-UTR intron was present in the longest isoform of ( ) mRNA 3'-UTR contains six Stau2 crosslink clusters, four of which are in this retained 3'-UTR intron. The mRNA localized to neuronal dendrites, while lack of the 3'-UTR intron impaired its dendritic localization. Importantly, Stau2 mediates this dendritic localization via the 3'-UTR intron, without affecting its stability. Also, NMDA-mediated synaptic activity specifically promoted the dendritic mRNA localization of the isoform, while inhibition of synaptic activity reduced it substantially. Together, our results identify the retained intron as a critical element in recruiting Stau2, which then allows for the localization of mRNA to distal dendrites.

Trypanosomatids are unicellular eukaryotes responsible for severe diseases in humans. They exhibit a number of remarkable biological phenomena, especially at the RNA level. During their life cycles, they alternate between a mammalian host and an insect vector and undergo profound biochemical and morphological transformations in order to adapt to the different environments they find within one or the other host species. These changes are orchestrated by specific gene expression programs. In contrast to other organisms, trypanosomatids do not regulate RNA polymerase II-dependent transcription initiation. Evidence so far indicates that the main control points in gene expression are mRNA degradation and translation. Recent studies have shown that RNA-binding proteins (RBPs) play a critical role in the developmental regulation of mRNA and protein abundance. RBPs seem to bind to specific subsets of mRNAs encoding functionally related proteins. These ribonucleoprotein complexes may represent posttranscriptional operons or regulons that are able to control the fate of multiple mRNAs simultaneously. We suggest that trypanosomatids transduce environmental signals into mRNA and protein abundance through posttranslational modification of RBPs.

mRNA transport restricts translation to specific subcellular locations, which is the basis for many cellular functions. However, the precise process of mRNA sorting to synapses in neurons remains elusive. Here we use Rgs4 mRNA to investigate 3′-UTR-dependent transport by MS2 live-cell imaging. The majority of observed RNA granules display 3′-UTR independent bidirectional transport in dendrites. Importantly, the Rgs4 3′-UTR causes an anterograde transport bias, which requires the Staufen2 protein. Moreover, the 3′-UTR mediates dynamic, sustained mRNA recruitment to synapses. Visualization at high temporal resolution enables us to show mRNA patrolling dendrites, allowing transient interaction with multiple synapses, in agreement with the sushi-belt model. Modulation of neuronal activity by either chemical silencing or local glutamate uncaging regulates both the 3′-UTR-dependent transport bias and synaptic recruitment. This dynamic and reversible mRNA recruitment to active synapses would allow translation and synaptic remodeling in a spatially and temporally adaptive manner.

It is widely believed that activity-dependent synaptic plasticity is the basis for learning and memory. Both processes are dependent on new protein synthesis at the synapse. Here, we describe a mechanism how dendritic mRNAs are transported and subsequently translated at activated synapses. Furthermore, we present the players involved in the regulation of local dendritic translation upon neuronal stimulation and their molecular interplay that maintain local proteome homeostasis. Any dysregulation causes several types of neurological disorders including muscular atrophies, cancers, neuropathies, neurodegenerative, and cognitive disorders.

Regulation of RNA polymerase II transcription initiation is apparently absent in trypanosomes. Instead, these eukaryotes control gene expression mainly at the post-transcriptional level. Regulation is exerted through the action of numerous RNA-binding proteins that modulate mRNA processing, turnover, translation and localization. In this work we show that the RNA-binding protein DRBD3 resides in the cytoplasm, but localizes to the nucleus upon oxidative challenge and to stress granules under starvation conditions. DRBD3 associates with other proteins to form a complex, the composition of which is altered by cellular stress. Interestingly, target mRNAs remain bound to DRBD3 under stress conditions. Our results suggest that DRBD3 transports regulated mRNAs within the cell in the form of ribonucleoprotein complexes that are remodeled in response to environmental cues.