LARP1-DM15/Sgt is a reader for cap-adjacent 2`-O-ribose methylation in TOP ribosomal protein mRNAs required for localization to synapses
- 1University of Manchester
Abstract
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.
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BibTeX
@misc{tian2026larp1dm15sgt,
title = {{LARP1-DM15/Sgt is a reader for cap-adjacent 2`-O-ribose methylation in TOP ribosomal protein mRNAs required for localization to synapses}},
author = {Y. W. Tian and Y. Hadzhiev and G. Abis and M. Dodel and E. Alard and D. McQuarrie and F. K. Mardakheh and M. Conte and F. Mueller and M. Soller},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.17.752351},
url = {https://www.biorxiv.org/content/10.64898/2026.09.17.752351v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - LARP1-DM15/Sgt is a reader for cap-adjacent 2`-O-ribose methylation in TOP ribosomal protein mRNAs required for localization to synapses
AU - Y. W. Tian
AU - Y. Hadzhiev
AU - G. Abis
AU - M. Dodel
AU - E. Alard
AU - D. McQuarrie
AU - F. K. Mardakheh
AU - M. Conte
AU - F. Mueller
AU - M. Soller
PY - 2026
DA - 2026/09/17
PB - bioRxiv
DO - 10.64898/2026.09.17.752351
UR - https://www.biorxiv.org/content/10.64898/2026.09.17.752351v1
AB - 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.
ER -