Messenger RNA delivery to mitoribosomes – hints from a bacterial toxin. (11th May 2020)

• Record Type: Journal Article
• Authors: Bruni, Francesco; Proctor‐Kent, Yasmin; Lightowlers, Robert N.; Chrzanowska‐Lightowlers, Zofia M.
• Is Part Of: FEBS journal. Volume 288:Number 2(2021)
• Page Start: 437
• Page End: 451
• Publication Date: 2020-05-11
• Subjects: LRPPRC/SLIRP -- mitochondrial mRNA turnover -- mitoribosome -- SRL -- VapC20; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 572
• DOI: 10.1111/febs.15342
• Languages: English
• ISSNs: 1742-464X

Abstract

Abstract : In mammalian mitochondria, messenger RNA is processed and matured from large primary transcripts in structures known as RNA granules. The identity of the factors and process transferring the matured mRNA to the mitoribosome for translation is unclear. Nascent mature transcripts are believed to associate initially with the small mitoribosomal subunit prior to recruitment of the large subunit to form the translationally active monosome. When the small subunit fails to assemble, however, the stability of mt‐mRNA is only marginally affected, and under these conditions, the LRPPRC/SLIRP RNA‐binding complex has been implicated in maintaining mt‐mRNA stability. Here, we exploit the activity of a bacterial ribotoxin, VapC20, to show that in the absence of the large mitoribosomal subunit, mt‐mRNA species are selectively lost. Further, if the small subunit is also depleted, the mt‐mRNA levels are recovered. As a consequence of these data, we suggest a natural pathway for loading processed mt‐mRNA onto the mitoribosome. Abstract : The late stages of the life cycle of mitochondrial messenger RNAs (mt‐mRNAs) are still poorly understood; in particular, protection of mt‐RNAs, their recognition by mitochondrial ribosomes and set‐up of translation. Now, Francesco Bruni and colleagues use the bacterial endoribonuclease VapC20 – inducibly expressed in a cell line – as a novel tool to selectively degrade a part of a large subunit of the mitochondrial ribosome. Using this cellular model, they propose that formation of mRNA‐associated ribosomes is needed for mt‐mRNA stability after transfer from the mt‐mRNA‐stabilising LRPPRC/SLIRP complex. For further information, please also see our Commentary by Borowski and Szczesny: https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.15435 .