Biology subjects

Murcha, M. W.

Publications and source records attributed to Murcha, M. W..

4 recordsLinked to original sources

bioRxiv2026

iGEX: an interactive Gene EXpression exploration platform for the analysis of transcriptomic and proteomic datasets

High-throughput transcriptomic and proteomic studies have generated a rapidly expanding collection of publicly available datasets. However, extracting biological insight from these resources often requires researchers to repeatedly download, reformat, integrate and analyse individual files using specialised tools. This process is time-consuming and often requires coding expertise. Here, we present iGEX, an interactive exploration platform that can incorporate publicly available and user-generated transcriptomic and proteomic datasets into a single visual workspace to simplify the analysis of multiple transcripts and/or proteins across numerous datasets. iGEX enables researchers to select gene/protein targets and experiments and compare expression patterns across biological conditions and experiments. User-generated data can be examined alongside numerous public resources such as EMBL-EBI Expression Atlas, Bgee, and PaxDb to determine whether any observed patterns are evident across experiments, species or experimental contexts. Users can visualise and move directly between data tables, principal component analysis, expression and correlation heatmaps, hierarchical clustering and volcano plots, all of which are editable and downloadable.

bioinformatics↗

bioRxiv2023

Structural analysis of the Sterile alpha motif (SAM) domain of the Arabidopsis mitochondrial tRNA import receptor

Mitochondria are membrane bound organelles of endosymbiotic origin with limited protein coding capacity. As a consequence, the continual import of nuclear-encoded protein and nucleic acids such as DNA and small non-coding RNA is required and essential for maintaining organelle mass, number and activity. As plant mitochondria do not encode all the necessary tRNA types required, the import of cytosolic tRNA is vital for organelle maintenance. Recently, two mitochondrial outer membrane proteins, named Tric1 and Tric2, for tRNA import component, were shown to be involved in the import of cytosolic tRNA. Tric1/2 binds tRNAala via conserved residues in the C-terminal Sterile Alpha Motif (SAM) domain. Here we report the X-ray crystal structure of the Tric1 SAM domain. We identified the ability of the SAM domain to form a helical superstructure with 6 SAM domains per helical turn and key amino acid residues responsible for its formation. We determined that the oligomerization of Tric1 SAM domain was essential for protein function whereby mutation of Gly241 resulted in the disruption of the oligomer and the loss of RNA binding capability in Tric1. Furthermore, complementation of Arabidopsis thaliana Tric1/2 knockout lines with a mutated Tric1 failed to restore the defective plant phenotype suggesting the oligomerization is essential for function in planta. AlphaFold2 structure prediction of the SAM domain and Tric1 support a cyclic hexamer generating a pore of sufficient dimensions to transfer tRNA across the mitochondrial membrane. Our results highlight the importance of oligomerization of Tric1 for protein function.

biochemistry↗

bioRxiv2023

FTSH3 facilitates complex I degradation through a direct interaction with the complex I subunit PSST

Complex I (NADH dehydrogenase), the largest complex involved in mitochondrial oxidative phosphorylation is composed of nuclear and mitochondrial encoded subunits. Its assembly requires sequential addition of subdomains and modules. As it is prone to oxidative damage, complex I subunits continually undergo proteolysis and turnover. We describe the mechanism by which complex I abundance is regulated in a complex I deficient mutant. Using a forward genetic approach we have identified that the complex I Q-module domain subunit PSST, interacts with FTSH3 (Filamentous Temperature Sensitive H3) to mediate the disassembly of the matrix arm domain module for proteolysis and turnover as a means of protein quality control. We show the direct interaction of FTSH3 with PSST and identify the amino acid residues required for this interaction. It is the ATPase function of FTSH3 that is required for the interaction, as the mutation can be compensated by a proteolytically inactive form of FTSH3. Furthermore, it cannot be compensated by FTSH10 that is also located in mitochondria, as the latter does not interact with PSST. This study reveals the mechanistic process at the resolution of the residues involved of how FTSH3 recognises complex I for degradation.

plant biology↗

bioRxiv2021

Inhibition of chloroplast translation as a new target for herbicides

The rise in herbicide resistance over recent decades threatens global agriculture and food security and so discovery of new modes of action is increasingly important. Here we reveal linezolid, an oxazolidinone antibiotic that inhibits microbial translation, is also herbicidal. To validate the herbicidal mode of action of linezolid we confirmed its micromolar inhibition is specific to chloroplast translation and did not affect photosynthesis directly. To assess the herbicide potential of linezolid, testing against a range of weed and crop species found it effective pre- and post-emergence. Using structure-activity analysis we identified the critical elements for herbicidal activity, but importantly also show, using antimicrobial susceptibility assays, that separation of antibacterial and herbicidal activities was possible. Overall these results validate chloroplast translation as a viable herbicidal target.

plant biology↗