Identification of LACTB2, a metallo-β-lactamase protein, as a human mitochondrial endoribonuclease

Levy, Shiri; Allerston, C.K.; Liveanu, Varda; Habib, Mouna; Gileadi, O.; Schuster, Gadi

doi:10.1093/nar/gkw050

Cited by 41 publications

(31 citation statements)

References 86 publications

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“…More recently, an endoribonuclease, LACTB2, has been identified in mammalian mitochondria. This protein has been thoroughly characterised in vitro, including high resolution structural data, but its physiological function remains unclear (Levy et al 2016). …”

Section: Post-translation Eventsmentioning

confidence: 99%

The process of mammalian mitochondrial protein synthesis

Mai

Chrzanowska-Lightowlers

Lightowlers

2016

Cell Tissue Res

108

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Oxidative phosphorylation (OXPHOS) is the mechanism whereby ATP, the major energy source for the cell, is produced by harnessing cellular respiration in the mitochondrion. This is facilitated by five multi-subunit complexes housed within the inner mitochondrial membrane. These complexes, with the exception of complex II, are of a dual genetic origin, requiring expression from nuclear and mitochondrial genes. Mitochondrially encoded mRNA is translated on the mitochondrial ribosome (mitoribosome) and the recent release of the near atomic resolution structure of the mammalian mitoribosome has highlighted its peculiar features. However, whereas some aspects of mitochondrial translation are understood, much is to be learnt about the presentation of mitochondrial mRNA to the mitoribosome, the biogenesis of the machinery, the exact role of the membrane, the constitution of the translocon/insertion machinery and the regulation of translation in the mitochondrion. This review addresses our current knowledge of mammalian mitochondrial gene expression, highlights key questions and indicates how defects in this process can result in profound mitochondrial disease.

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Section: Post-translation Eventsmentioning

confidence: 99%

The process of mammalian mitochondrial protein synthesis

Mai

Chrzanowska-Lightowlers

Lightowlers

2016

Cell Tissue Res

108

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“…LACTB2 (metallo-β-lactamase protein) is a mitochondrial endoribonuclease that cleaves ssRNA but not dsRNA or ssDNA. LACTB2 is essential for mitochondrial function and cell viability and its overexpression in cultured cells causes a reduction in many mitochondrial transcripts (Levy et al, 2016). Mitochondrial dysfunction has been implicated in Alzheimer's disease and across several other neurodegenerative disorders such as Parkinson's and Huntington's disease (Perez Ortiz and Swerdlow, 2019) and across neuropsychiatric disorders such as bipolar disorder, depression and Schizophrenia (Wu et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Monocyte-specific changes in gene expression implicateLACTB2andPLIN2in Alzheimer’s disease

Harwood

Leonenko

Sims

et al. 2020

Preprint

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More than 50 genetic loci have been identified as being associated with Alzheimer's disease (AD) from genome-wide association studies (GWAS) and many of these are involved in immune pathways and lipid metabolism. Therefore, we performed a transcriptome-wide association study (TWAS) of immune-relevant cells, to study the mis-regulation of genes implicated in AD. We used expression and genetic data from naive and induced CD14+ monocytes and two GWAS of AD to study genetically controlled gene expression in monocytes at different stages of differentiation and compared the results with those from TWAS of brain and blood. We identified nine genes with statistically independent TWAS signals, seven are known AD risk genes from GWAS: BIN1, PTK2B, SPI1, MS4A4A, MS4A6E, APOE and PVR and two, LACTB2 and PLIN2/ADRP, are novel candidate genes for AD. Three genes, SPI1, PLIN2 and LACTB2, are TWAS significant specifically in monocytes. LACTB2 is a mitochondrial endoribonuclease and PLIN2/ADRP associates with intracellular neutral lipid storage droplets (LSDs) which have been shown to play a role in the regulation of the immune response. Notably, LACTB2 and PLIN2 were not detected from GWAS alone.

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“…However, RNase Z (ELAC2), which is a CPSF homologue, is a mitochondrial endoribonuclease that processes the 3 end of tRNA precursors. LACTB2 is an endoribonuclease that is present in human mitochondria, belongs to the MBL protein super family, and is possibly involved in RNA quality control [57]. RNase P, which is responsible for the 5 -end processing of tRNAs, is an additional mitochondrial endoribonuclease.…”

Section: Ribonuclease J and β-Casp Proteinsmentioning

confidence: 99%

Plant Ribonuclease J: An Essential Player in Maintaining Chloroplast RNA Quality Control for Gene Expression

Hotto

Stern

Schuster

2020

Plants

Self Cite

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RNA quality control is an indispensable but poorly understood process that enables organisms to distinguish functional RNAs from nonfunctional or inhibitory ones. In chloroplasts, whose gene expression activities are required for photosynthesis, retrograde signaling, and plant development, RNA quality control is of paramount importance, as transcription is relatively unregulated. The functional RNA population is distilled from this initial transcriptome by a combination of RNA-binding proteins and ribonucleases. One of the key enzymes is RNase J, a 5′→3′ exoribonuclease and an endoribonuclease that has been shown to trim 5′ RNA termini and eliminate deleterious antisense RNA. In the absence of RNase J, embryo development cannot be completed. Land plant RNase J contains a highly conserved C-terminal domain that is found in GT-1 DNA-binding transcription factors and is not present in its bacterial, archaeal, and algal counterparts. The GT-1 domain may confer specificity through DNA and/or RNA binding and/or protein–protein interactions and thus be an element in the mechanisms that identify target transcripts among diverse RNA populations. Further understanding of chloroplast RNA quality control relies on discovering how RNase J is regulated and how its specificity is imparted.

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Identification of LACTB2, a metallo-β-lactamase protein, as a human mitochondrial endoribonuclease

Cited by 41 publications

References 86 publications

The process of mammalian mitochondrial protein synthesis

The process of mammalian mitochondrial protein synthesis

Monocyte-specific changes in gene expression implicateLACTB2andPLIN2in Alzheimer’s disease

Plant Ribonuclease J: An Essential Player in Maintaining Chloroplast RNA Quality Control for Gene Expression

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