A variant rRNA serves as a translational repressor in Plasmodium falciparum

Abstract

Ribosome composition can vary through differences in associated proteins, post-transcriptional and post-translational modifications. Such heterogeneity enables ribosomes to respond to environmental1 or pathological2,3 conditions, and modulate localized translation4. A long-standing observation has also been the differential expression of variant ribosomal RNA (rRNA) alleles across developmental5-7 or cellular states8-14. Yet how exchanging the catalytic ribosome core could regulate translational outcomes remains unknown. Here, we report the functional characterization of a genomically-encoded, divergent rRNA that serves as a dominant-negative repressor of translation during host-to-vector transmission in the human malaria parasite. This allele only encodes for large subunit rRNAs, lacks ITS2 splicing, yet retains conserved rRNA modification and folding patterns alongside vast expansion segments. The resulting large subunit engages mRNA at translation start sites but appears to elongate inefficiently, likely due to divergences in the peptidyl transferase center obstructing the exit tunnel. Through its precisely timed transcription immediately after transmission, this rRNA represses mRNAs that were highly translated in the human, facilitating the transition of the translational program for mosquito-stage development. Our data identify a repressive ribosome population whose antagonistic function is encoded by an independently evolved, variant rRNA allele, defining the conceptual foundation for an additional layer of inherent translational regulation.