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LARP4 Is an RNA-Binding Protein That Binds Nuclear-Encoded Mitochondrial mRNAs To Promote Mitochondrial Function

ABSTRACT: Mitochondria-associated RNA-binding proteins have emerged as key contributors to mitochondrial biogenesis and homeostasis. With few examples known, we set out to identify RBPs that regulate nuclear-encoded mitochondrial mRNAs. Our systematic analysis of RNA targets of 150 RBPs identified RBPs with a preference for binding NEM mRNAs, including LARP4, a La RBP family member. We show that LARP4s targets are particularly enriched in mRNAs that encode respiratory chain complex proteins and mitochondrial ribosome proteins across multiple human cell lines. Through quantitative proteomics, we demonstrate that depletion of LARP4 leads to a significant reduction in RCCP and MRP protein levels. Furthermore, we show that LARP4 depletion reduces mitochondrial function, and that LARP4 re-expression rescues this phenotype. Our findings shed light on a novel function for LARP4 as an RBP that binds to and positively regulates NEM mRNAs to promote mitochondrial respiratory function.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Tony Hunter

PROVIDER: MSV000093340 | MassIVE | Wed Nov 08 17:56:00 GMT 2023

SECONDARY ACCESSION(S): PXD046798

REPOSITORIES: MassIVE

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LARP4 Is an RNA-Binding Protein That Binds Nuclear-Encoded Mitochondrial mRNAs To Promote Mitochondrial Function

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