YbeY is required for ribosome small subunit assembly and tRNA processing in human mitochondria

Abstract

Mitochondria contain their own translation apparatus which enables them to produce the polypeptides encoded in their genome. The mitochondrially-encoded RNA components of the mitochondrial ribosome require various post-transcriptional processing steps. Additional protein factors are required to facilitate the biogenesis of the functional mitoribosome. We have characterised a mitochondrially-localized protein, YbeY, which interacts with the assembling mitoribosome through the small subunit. Loss of YbeY leads to a severe reduction in mitochondrial translation and a loss of cell viability, caused by less accurate mitochondrial mt-tRNASer(AGY) processing from the primary transcript and an accumulation of immature mitochondrial small subunit. Our results suggest that YbeY performs a dual function in mitochondria coupling tRNA processing to mitoribosome biogenesis.

YbeY, éminence grise of ribosome biogenesis

“…1). The two studied eukaryotic homologuesfrom Arabidopsis thaliana and humanlocalise in chloroplasts and mitochondria, respectively [2][3][4]. Additionally, the YbeY proteins of Plasmodium falciparum (Apixomplexa) and Trypanosoma brucei (Discoba) reside in the apicoplast and the kinetoplast, correspondingly [5,6], supporting the notion that members of this protein family operate in bacterial-type genetic systems and have been carried over into the eukaryotic kingdom along with the ancestors of the modern plastids and mitochondria.…”

“…Nevertheless, the SSU assembly is impaired, with several head and platform proteins depleted or completely missing [3,4,20,21].…”

“…This announces two kinds of problems. First, the SSU becomes unstable and undergoes rapid degradation [3,4,9,16,22]. For example, in bacteria like E. coli aberrant, unspecific internal cleavages sever the 3'-minor domain of 16S rRNA [16,23].…”

“…Besides this common 'phenotypic core', a few interesting species-specific alterations have been reported (Table 1). In E. coli and chloroplasts, the large subunit (LSU) rRNAs also show maturation defects [2,15], whereas in C. glutamicum and the human mitochondria, the SRP RNA and a tRNA Ser , respectively, are significantly misprocessed in the absence of YbeY [4,37]. Based on genetic and/or biochemical experiments, new roles for E. coli YbeY in rRNA transcription antitermination [38] and the turnover of defective or damaged ribosomes [16,17,23,39] have been proposed.…”

“…It is also essential in Plasmodium [10]. In human, YBEY knockout severely impairs mitochondrial respiration [3,4]; elevated YBEY expression has been associated with breast cancer, whereas a loss-of-function variant is a candidate driver of Lynch syndrome [11][12][13]. Surprisingly, after nearly two decades of research, our understanding of how YbeY works, why it is so important for bacteria and the derived eukaryotic organelles remains rather limited.…”