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McQuarrie, D.

Publications and source records attributed to McQuarrie, D..

2 recordsLinked to original sources

LARP1-DM15/Sgt is a reader for cap-adjacent 2`-O-ribose methylation in TOP ribosomal protein mRNAs required for localization to synapses

The most prominent mRNA modification in animals and many of their parasites is 2`-O-ribose methylation of cap-adjacent nucleotides (cOMe) introduced by cap-methyl transferases (CMTrs). How these modifications impact on gene expression and are decoded by reader proteins, however, remains uncertain. Through analysis of transcriptional start-site usage, we discovered a bias in ribosomal protein mRNAs starting with the Terminal Oligo Pyrimidine (TOP) motif, but not other TOP mRNAs in the absence of cOMe. cOMe stabilizes TOP mRNAs, enhances binding of the LARP1-DM15 domain to the TOP mRNA 5` end and is assisted by the tetratricopeptide domain-containing protein Sgt/SGTA/B. This conserved complex is required for localization of TOP ribosomal protein mRNAs to Drosophila synapses. Our study reveals an mRNA methylation-mediated mechanism to maintain local protein synthesis remote from the nucleus for sustained synaptic functions.

molecular biology↗

Memory consolidation in honey bees is enhanced by down-regulation of Down Syndrome Cell Adhesion Molecule and changes its alternative splicing

Down syndrome cell adhesion molecule (Dscam) gene encodes a cell adhesion molecule required for neuronal wiring. A remarkable feature of invertebrate Dscam is massive alternative splicing generating thousands of different isoforms from three variable clusters of alternative exons. Dscam expression and diversity arising from alternative splicing have been studied during development, but whether they exert functions in differentiated brains has not been determined. Here, using honey bees, we find that Dscam expression is critically linked to memory retention as reducing expression by RNAi enhances memory after reward learning in adult worker bees. Moreover, alternative splicing of Dscam is altered in all three variable clusters after learning. Since identical Dscam isoforms engage in homophilic interactions, these results suggest a mechanism to alter inclusion of variable exons during memory consolidation to modify neuronal connections for memory retention.

neuroscience↗