Biology subjects

Abis, G.

Publications and source records attributed to Abis, G..

3 recordsLinked to original sources

bioRxiv2026

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↗

bioRxiv2025

Structural mechanisms of drebrin-mediated F-actin network modulation

Drebrin modulates F-actin networks and links them to other intracellular components, regulating crucial processes including neuritogenesis, synaptic plasticity, virus internalisation and cancer invasion. Using single-particle cryo-EM we characterise drebrins interaction with F-actin through two separate conserved actin binding domains (ABD1 and ABD2), revealing structural bases for its F-actin-modulating properties. We describe a multimodal interaction where drebrins ABD1 can adopt two conformations and a long flexible loop connecting to ABD2 allows the two ABDs to occupy multiple relative positions along F-actin. Despite harbouring two separated ABDs, we find that drebrin is not a strong direct F-actin bundler. Drebrins ABDs bind across multiple actin protomers and their subdomains and modify the longitudinal inter-protomer interface, explaining their F-actin stabilising properties. Furthermore, we show drebrins binding site on F-actin is shared with other critical actin-binding and regulatory proteins, explaining their competitive displacement.

biochemistry↗

bioRxiv2024

An intrinsically disordered RNA-binding region provides local target selectivity and is essential for LARP6 function.

Intrinsically disordered regions (IDRs) are prevalent in RNA-binding proteins (RBPs), yet their roles in RNA interactions remain poorly defined. Here, we examined the structured and disordered RNA-binding activities of LARP6, an RBP with a diverse RNA-binding repertoire. Using mass spectrometry-based RNA interaction mapping in living cells, we identified direct LARP6-RNA contacts within both the structured La-module and its flanking IDRs. Mutagenesis combined with individual-nucleotide resolution UV crosslinking and immunoprecipitation (iCLIP) revealed the La-module, but not the IDRs, as essential for LARP6 binding to RNA. Deletion of the N-terminal IDR broadened the footprints of LARP6 on RNA, uncovering a role in RNA-binding selectivity. Mechanistically, this is achieved through restricting the conformational flexibility of the adjacent La-module. The IDR-mediated RNA-binding selectivity is critical for LARP6-driven cancer cell viability and invasion. Our findings uncover a previously unrecognised critical function for IDRs in promoting selective RBP-RNA interactions, which operates through conformational restriction.

biochemistry↗