Publication Date
5-16-2024
Journal
RNA
DOI
10.1261/rna.079999.124
PMID
38448244
PMCID
PMC11098466
PubMedCentral® Posted Date
6-30-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Mitochondria, Humans, Animals, Mitochondrial Membranes, RNA, Mitochondrial, RNA-Binding Proteins, RNA, Messenger, RNA, RNA Transport, RNA, Transfer, Protein Biosynthesis, Mitochondrial Proteins, imaging, mitochondrial biology, RNA subcellular localization, technologies, transcriptomics
Abstract
The mammalian mitochondrial proteome comprises over 1000 proteins, with the majority translated from nuclear-encoded messenger RNAs (mRNAs). Mounting evidence suggests many of these mRNAs are localized to the outer mitochondrial membrane (OMM) in a pre- or cotranslational state. Upon reaching the mitochondrial surface, these mRNAs are locally translated to produce proteins that are cotranslationally imported into mitochondria. Here, we summarize various mechanisms cells use to localize RNAs, including transfer RNAs (tRNAs), to the OMM and recent technological advancements in the field to study these processes. While most early studies in the field were carried out in yeast, recent studies reveal RNA localization to the OMM and their regulation in higher organisms. Various factors regulate this localization process, including RNA sequence elements, RNA-binding proteins (RBPs), cytoskeletal motors, and translation machinery. In this review, we also highlight the role of RNA structures and modifications in mitochondrial RNA localization and discuss how these features can alter the binding properties of RNAs. Finally, in addition to RNAs related to mitochondrial function, RNAs involved in other cellular processes can also localize to the OMM, including those implicated in the innate immune response and piRNA biogenesis. As impairment of messenger RNA (mRNA) localization and regulation compromise mitochondrial function, future studies will undoubtedly expand our understanding of how RNAs localize to the OMM and investigate the consequences of their mislocalization in disorders, particularly neurodegenerative diseases, muscular dystrophies, and cancers.