ABCE1

ABCE1
Identifiers
Aliases	ABCE1, ABC38, OABP, RLI, RNASEL1, RNASELI, RNS4I, ATP binding cassette subfamily E member 1, RLI1
External IDs	OMIM: 601213 MGI: 1195458 HomoloGene: 2205 GeneCards: ABCE1
Gene location (Human) Chr. Chromosome 4 (human)[1] Band 4q31.21 Start 145,098,288 bp[1] End 145,129,524 bp[1]
Gene location (Mouse) Chr. Chromosome 8 (mouse)[2] Band 8|8 C1 Start 80,410,091 bp[2] End 80,438,369 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in islet of Langerhans Achilles tendon stromal cell of endometrium ganglionic eminence secondary oocyte body of pancreas rectum appendix thymus gallbladder Top expressed in cumulus cell abdominal wall lacrimal gland maxillary prominence dermis primitive streak corneal stroma hair follicle superior surface of tongue vas deferens More reference expression data BioGPS n/a
Gene ontology Molecular function nucleotide binding ATPase activity protein binding iron ion binding ribosomal small subunit binding ATP binding endoribonuclease inhibitor activity Cellular component cytoplasm mitochondrial matrix membrane mitochondrion eukaryotic translation initiation factor 3 complex cytosol Biological process viral process ribosomal subunit export from nucleus translational termination negative regulation of endoribonuclease activity translational initiation regulation of type I interferon-mediated signaling pathway defense response to virus Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 6059 24015 Ensembl ENSG00000164163 ENSMUSG00000058355 UniProt P61221 P61222 RefSeq (mRNA) NM_002940 NM_001040876 NM_015751 RefSeq (protein) NP_001035809 NP_002931 NP_056566 Location (UCSC) Chr 4: 145.1 – 145.13 Mb Chr 8: 80.41 – 80.44 Mb PubMed search [3] [4]
Wikidata
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ATP-binding cassette sub-family E member 1 (ABCE1) also known as RNase L inhibitor (RLI) is an enzyme that in humans is encoded by the ABCE1 gene.

ABCE1 is an ATPase that is a member of the ATP-binding cassette (ABC) transporters superfamily and OABP subfamily.^[5]

ABCE1 inhibits the action of ribonuclease L. Ribonuclease L normally binds to 2-5A (5'-phosphorylated 2',5'-linked oligoadenylates) and inhibits the interferon-regulated 2-5A/RNase L pathway, which is used by viruses. ABCE1 heterodimerize with ribonuclease L and prevents its interaction with 2-5A, antagonizing the anti-viral properties of ribonuclease L,^[6] and allow the virus to synthesize viral proteins. It has also been implicated to have an effect in tumor cell proliferation and antiapoptosis.^[7]

ABCE1 is an essential and highly conserved protein that is required for both eukaryotic translation initiation as well as ribosome biogenesis. The most studied homologues are Rli1p in yeast and Pixie in Drosophila.

Structure[edit]

RLI is a 68 kDa cytoplasmic protein found in most eukaryota and archae. Since the crystal structure for RLI has not yet been determined, all that is known has been inferred from protein sequencing. The protein sequences between species is very well conserved, for example Pixie and yeast Rli1p are 66% identical, and Rli1p and human RLI are 67% identical.

RLI belongs to the ABCE family of ATP-binding cassette (ABC) proteins. ABC proteins typically also contain a transmembrane region, and utilize ATP to transport substrates across a membrane, however RLI is unique in that it is a soluble protein that contains ABC domains. RLI has two C-terminal ABC domains; upon binding ATP they form a characteristic "ATP-sandwich," with two ATP molecules sandwiched between the two dimerized ABC domains. Hydrolysis of ATP allows the dimer to dissociate in a fully reversible process. Incubation of the protein with a non-hydrolyzable ATP analogue or a mutation of the ABC domain causes a complete loss of protein function.

RLI also has a cysteine-rich N-terminal region that is predicted to tightly bind two [4Fe-4S] clusters. Mutation of this region, or depletion of available Fe/S clusters, renders the protein unable to function, and loss of cell viability, making RLI the only known essential cytoplasmic protein dependent on Fe/S cluster biosynthesis in the mitochondria. The function of the Fe/S clusters is unknown, although it has been suggested that they regulate the ABC domains in response to a change in the redox environment, for example in the presence of reactive oxygen species.^[8]

Function[edit]

RLI and its homologues in yeast and Drosophila have two major identified functions: translation initiation and ribosome biogenesis. In addition, human RLI is a known inhibitor of RNAse L. This was the first activity identified and the source of its name (RNAse L Inhibitor).

Translation Initiation[edit]

Translation initiation is an essential process required for proper protein expression and cell viability. Rli1p has been found to co-purify with eukaryotic initiation factors, specifically eIF2, eIF5, and eIF3, as well as the 40S subunit of the ribosome. These initiation factors must associate with the ribosome in stoichiometric proportions, while Rli1p is required in catalytic amounts. The following mechanism for the process has been proposed: One ABC domain binds the 40S subunit, while the other binds an initiation factor. Binding of ATP allows for dimerization, which subsequently brings the initiation factor and ribosomal subunit in close enough contact to associate. ATP hydrolysis releases the two substrates and allows the cycle to begin again. This model is similar to one that has been proposed for DNA repair enzymes with ABC domains, in which each domain binds either side of a broken piece of DNA, with hydrolysis allowing the pieces to be brought together and subsequently repaired.^[9]

Ribosome recycling[edit]

Recycling is essential for ribosomes to become usable again after translating an mRNA or stalling. In both eukaryotes and archaea, ABCE1 is responsible for splitting a ribosome that has been bound to Pelota or its paralog eRF1. The exact movements leading to the split is not well understood.^[10][11]

Ribosome biogenesis[edit]

RLI and its homologues are also thought to play a role in ribosome biogenesis, nuclear export, or both. They have been found in the nucleus associated with the 40S and 60S subunits, as well as Hcr1p, a protein required for rRNA processing. It has been shown that the Fe/S clusters are necessary for ribosome biogenesis and/or nuclear export, although the exact mechanism is unknown.

RNAse inhibitor[edit]

Human RLI was first identified because of its ability to inhibit RNAse L, which plays a crucial role in antiviral activity in mammals. This cannot account for the conservation of the protein in all other organisms, since only mammals have the RNAse L system. It has been suggested that RLI in lower eukaryotes functions by inhibiting RNAses involved in ribosomal biosynthesis, thereby regulating the process.^[12]

Role in mitochondria[edit]

The mitochondria's energetic and metabolic functions have been established to be non-essential for yeast cell viability. The only function that has been implicated in being necessary for survival is the biosynthesis of Fe/S clusters. RLI is the only known essential cytoplasmic Fe/S protein that is absolutely dependent on the mitochondrial Fe/S synthesis and export system for proper maturation. Rli1p is therefore a novel link between the mitochondria and ribosome function and biosynthesis, and therefore the viability of the cell.

References[edit]

External links[edit]

• ABCE1 at NCBI AceView genes
• ABCE1 at GeneCards
• P61221 UniProt