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Activity-dependent expression of immediate early genes (IEGs) is critical for long-term synaptic remodeling and memory. It remains unknown how IEGs are maintained for memory despite rapid transcript and protein turnover. To address this conundrum, we monitored Arc , an IEG essential for memory consolidation. Using a knockin mouse where endogenous Arc alleles were fluorescently tagged, we performed real-time imaging of Arc mRNA dynamics in individual neurons in cultures and brain tissue. Unexpectedly, a single burst stimulation was sufficient to induce cycles of transcriptional reactivation in the same neuron. Subsequent transcription cycles required translation, whereby new Arc proteins engaged in autoregulatory positive feedback to reinduce transcription. The ensuing Arc mRNAs preferentially localized at sites marked by previous Arc protein, assembling a "hotspot" of translation, and consolidating "hubs" of dendritic Arc. These cycles of transcription-translation coupling sustain protein expression and provide a mechanism by which a short-lived event may support long-term memory. [Display omitted] • Reactivation of transcription drives cycling of the Arc gene in individual neurons • Feedback from new proteins reinduces Arc transcription in the next cycle • Arc mRNAs from later cycles localize to sites marked with previous Arc protein • Repetitive translation in hotspots consolidates dendritic Arc in selective hubs How are short-lived mRNAs and proteins maintained over time to impact long-term memory? Das et al. report that repetitive cycles of transcription and local translation of the immediate early gene Arc amplify a single burst stimulation over time to assemble Arc protein hubs, revealing a molecular mechanism that supports memory consolidation. [ABSTRACT FROM AUTHOR]

Summary: Ribosomal processing requires a series of endo- and exonucleolytic steps for the production of mature ribosomes, of which most have been described. To ensure ribosome synthesis, 3′ end formation of rRNA uses multiple nucleases acting in parallel; however, a similar parallel mechanism had not been described for 5′ end maturation. Here, we identify Rrp17p as a previously unidentified 5′–3′ exonuclease essential for ribosome biogenesis, functioning with Rat1p in a parallel processing pathway analogous to that of 3′ end formation. Rrp17p is required for efficient exonuclease digestion of the mature 5′ ends of 5.8SS and 25S rRNAs, contains a catalytic domain close to its N terminus, and is highly conserved among higher eukaryotes, being a member of a family of exonucleases. We show that Rrp17p binds late pre-60S ribosomes, accompanying them from the nucleolus to the nuclear periphery, and provide evidence for physical and functional links between late 60S subunit processing and export. [Copyright &y& Elsevier]

ASH1 mRNA localizes at the bud tip of late-anaphase yeast, resulting in accumulation of Ash1p in the daughter nucleus. We show that disruption of the secondary structure, but not the protein coding, of all four ASH1 localization elements resulted in RNA and protein delocalization. Localization of both was incrementally restored by replacement of each of the four elements. However, transposition of the elements to the 3′UTR reinstated the RNA, but not the protein, localization. Interestingly, the mutant ASH1 mRNA was translated more efficiently, suggesting that asymmetry of Ash1p resulted from translational inhibition by the localization elements. In support of this, Ash1p asymmetry could be rescued by slowing its translation. [Copyright &y& Elsevier]