Key result
Deletion of the La motif or RRM1 domains in the La protein of Trypanosoma brucei causes dysregulation of Q34-tRNA levels, demonstrating its role in controlling tRNA modification.
Why the study?
The function of the essential RNA-binding protein La is not completely clear, and the mechanisms controlling queuosine-modified tRNA levels in Trypanosoma brucei are not well understood.
The RNA-binding protein La controls Q34-tRNA levels and the balance of several tRNA modifications in Trypanosoma brucei, with the La motif and RRM1 domains being critical for this function.
La protein domains regulate Q34-tRNA in T. brucei; extends tRNA modification mechanisms and leaves open parasite-targeted interventions.
The RNA-binding protein La is found in most eukaryotes, and despite being essential in many organisms, its function is not completely clear. Trypanosoma brucei, the causative agent of human African trypanosomiasis, encodes a 'classical' La protein (TbLa) composed of a La-motif, two RNA recognition motifs (RRM1 and RRM2α), a C-terminal short basic motif (SBM), and a nuclear localization signal (NLS). In T. brucei, like in most eukaryotes, position 34 of tRNATyr, -Asp, -Asn and -His is modified with queuosine (Q34). The steady-state levels of queuosine-modified tRNA in the insect form (procyclic) of T. brucei can fluctuate dynamically depending on growth conditions, but the mechanism(s) controlling Q34 levels are not well understood. A well-established function of La is in precursor-tRNA 3'-end metabolism, but in this work, we demonstrate that La also controls Q34-tRNA levels. Individual domain deletions showed that while deletion of La motif or RRM1 causes dysregulation of Q34-tRNA levels, no other domain plays a similar role. We also show that La is important for the normal balance of several additional tRNA modifications. These findings are discussed in the context of substrate competition between La and modification enzymes, also highlighting subcellular localization as a key determinant of tRNA function.
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Gunaratne et al. (2025) studied Trypanosoma brucei infection. La protein domain deletions (La motif or RRM1) vs. Wild-type La protein or other domain deletions was evaluated on Q34-tRNA levels. Deletion of the La motif or RRM1 domains in the La protein of Trypanosoma brucei causes dysregulation of Q34-tRNA levels, demonstrating its role in controlling tRNA modification.
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