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LARP4 is an RNA-binding protein that binds nuclear-encoded mitochondrial mRNAs to promote mitochondrial function.

RNA (New York, N.Y.) · 2024 · Vol. 30 (3) · pp. 223-239

Abstract

Mitochondria-associated RNA-binding proteins (RBPs) 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 (NEMmRNAs). Our systematic analysis of RNA targets of 150 RBPs identified RBPs with a preference for binding NEMmRNAs, including LARP4, a La RBP family member. We show that LARP4's targets are particularly enriched in mRNAs that encode respiratory chain complex proteins (RCCPs) and mitochondrial ribosome proteins (MRPs) 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 NEMmRNAs to promote mitochondrial respiratory function.

Publication Types

["Journal Article"]

Keywords

MeSH Terms

["Humans", "Cell Line", "Mitochondria", "RNA-Binding Proteins", "Ribonucleoproteins", "RNA Recognition Motif Proteins"]

Funding

U24 HG009889 NHGRI NIH HHS (United States)
R01 HG004659 NHGRI NIH HHS (United States)
U41 HG009889 NHGRI NIH HHS (United States)
P30 CA014195 NCI NIH HHS (United States)
R01 CA082683 NCI NIH HHS (United States)
R01 CA080100 NCI NIH HHS (United States)
T32 GM007240 NIGMS NIH HHS (United States)
R35 CA242443 NCI NIH HHS (United States)

Linked Datasets (1)

GSE193134 GSE via ncbi_elink
GEO

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

Homo sapiens
8 data files
FileTypeSize
Hek293_WT_N_rep_1_S9_L007_R1_001.fastq.gz RIP-Seq 767.1 MB
Hek293_WT_N_rep_1_S9_L007_R1_001.fastq.gz RIP-Seq 767.1 MB
Hek293_WT_N_rep_2_S13_L007_R1_001.fastq.gz RIP-Seq 676.4 MB
Hek293_WT_N_rep_2_S13_L007_R1_001.fastq.gz RIP-Seq 676.4 MB
Hek293_WT_P_rep_1_S1_L007_R1_001.fastq.gz RIP-Seq 663.6 MB
Hek293_WT_P_rep_1_S1_L007_R1_001.fastq.gz RIP-Seq 663.6 MB
Hek293_WT_P_rep_2_S5_L007_R1_001.fastq.gz RIP-Seq 624.1 MB
Hek293_WT_P_rep_2_S5_L007_R1_001.fastq.gz RIP-Seq 624.1 MB

Potentially Related Datasets (2)

These accessions were text-mined from the PMC full text. They may be referenced for comparison, cited from other studies, or otherwise mentioned without being primary data for this paper.

MSV000093340 MASSIVE MassIVE

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

Analysis Pipelines (1)

eCLIP geo_data_processing GSE193134