Transfer RNA (tRNA)-derived small RNAs (tsRNAs) are newly identified non-coding small RNAs that have recently attracted attention due to their functional significance in both prokaryotes and eukaryotes. tsRNAs originated from the cleavage of precursor or mature tRNAs by specific nucleases. According to the start and end sites, tsRNAs can be broadly divided into tRNA halves (31–40 nucleotides) and tRNA-derived fragments (tRFs, 14–30 nucleotides). tsRNAs have been reported in multiple organisms to be involved in gene expression regulation, protein synthesis, and signal transduction. As a novel regulator, tsRNAs have also been identified in various protozoan parasites. The conserved biogenesis of tsRNAs in early-branching eukaryotes strongly suggests the universality of this machinery, which requires future research on their shared and potentially disparate biological functions. Here, we reviewed the recent studies of tsRNAs in several representative protozoan parasites including their biogenesis and the roles in parasite biology and intercellular communication. Furthermore, we discussed the remaining questions and potential future works for tsRNAs in this group of organisms.

Entamoeba histolytica , the protozoan parasite responsible for amoebiasis, deploys a complex array of virulence factors to establish infection and evade host defenses. Here, we identify KERP2 as a dual-function effector that regulates both parasite homeostasis and host cell remodeling. Bioinformatic analyses, cellular localization assays, and functional studies show that KERP2 localizes to the parasite nucleus, associates with chromatin, and modulates transcription, particularly regulating cysteine protease expression and sulfur metabolism. Concurrently, KERP2 is translocated into host epithelial cells, where it manipulates the G1/S transition, interacts with cytoskeletal regulators, and promotes actin remodeling, ultimately compromising epithelial barrier function. Our results elucidate how E. histolytica harnesses KERP2 to coordinate intracellular processes in the parasite while orchestrating pathogenic alterations in host cells. These insights shed light on a broader mechanism by which extracellular pathogens deploy multifunctional effectors to optimize virulence and adapt to diverse host environments, providing a valuable framework for studies on pathogen-host interactions beyond amoebiasis.

Entamoeba histolytica causes amoebiasis and damages intestinal epithelium, but how individual parasite factors coordinate parasite gene regulation with host remodeling is unclear. We investigate lysine- and glutamic acid-rich protein 2, a factor linked to the host brush border. Sequence analysis, imaging, and functional assays show that lysine- and glutamic acid-rich protein 2 accumulates in the parasite nucleus, binds AT-rich DNA, and modulates transcriptional programs related to Amoebiasis, including cysteine protease and sulfur metabolism. During parasite-epithelium contact, the protein enters host epithelial cells and is associated with increased deoxyribonucleic acid synthesis, altered cytoskeletal regulators, actin remodeling, and reduced barrier integrity. Here, we propose a working model in which lysine- and glutamic acid-rich protein 2 links parasite chromatin-associated regulation with host epithelial remodeling during contact. Notably, our data support host cytoskeletal and junctional phenotypes and do not yet establish a direct role for it in host chromatin regulation. Together, these observations suggest a potentially broader mechanism by which extracellular pathogens deploy effectors to optimize virulence and adapt to diverse host environments.