Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.26.5 (RNase P)
 1,348 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

RNase MRP is a ribonucleoprotein endoribonuclease that has been shown to cleave mitochondrial primer RNA sequences from a variety of sources. Most of the RNase MRP activity is found in the nucleus where it plays a role in the processing of 5.8S rRNA. A temperature-conditional point mutation in the yeast RNA component of the enzyme has been identified. This mutation results in a loss of normal rRNA processing at the nonpermissive temperature while cellular levels of the RNA component of RNase MRP remain stable. High-copy suppressor analysis of this point mutation was employed to identify interacting proteins. A unique suppressor, termed SNM1 (suppressor of nuclear mitochondrial endoribonuclease 1), was identified repeatedly. The SNM1 gene was localized to the right arm of chromosome IV, directly adjacent to the SNF1 gene, and it contains an open reading frame encoding a protein of 198 amino acids. The protein contains a leucine zipper motif, a zinc-cluster motif, and a serine/lysine-rich tail. The gene was found to be essential for viability in a yeast cell, consistent with it being a protein component of the RNase MRP ribonucleoprotein complex. Recombinant SNM1 protein binds RNA in both gel retardation and Northwestern assays. Antibodies raised against bacterially expressed proteins identified four separate species in yeast whole cell extracts. Antibodies directed against the SNM1 protein immunoprecipitated RNase MRP RNA from whole-cell extracts without precipitating the structurally and functionally related RNase P RNA. We propose that the SNM1 protein is an essential and specific component of the RNase MRP ribonucleoprotein complex, the first unique protein of this complex to be identified.
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PMID:Characterization of a unique protein component of yeast RNase MRP: an RNA-binding protein with a zinc-cluster domain. 795 20

Recently, we revealed that the cloverleaf structure of some eukaryotic tRNAs is not always stable in vitro, and the denatured structures of these tRNAs are sometimes detected in bacterial RNase P reactions. We have designated the unusual internal cleavage reaction of these tRNAs as hyperprocessing. We have developed this hyperprocessing strategy as a useful tool for examining the stability of the tRNA cloverleaf structure. There are some common features in such unstable, hyperprocessible tRNAs, and the criteria for the hyperprocessing reaction of tRNA are extracted. Metazoan initiator methionine tRNAs and lysine tRNAs commonly fit the criteria, and are predicted to be hyperprocessible. The RNase P reactions of two metazoan lysine tRNAs from Homo sapiens and Caenorhabditis elegans, which fit the criteria, resulted in resistance to the internal cleavage reaction, while one bacterial lysine tRNA from Acholeplasma laidlawii, which also fits the criteria, was internally cleaved by the RNase P. The results showed that the metazoan lysine tRNAs examined are very stable without base modifications even under in vitro conditions. We also examined the 3'-half short construct of the human lysine tRNA, and the results showed that this RNA was internally cleaved by the enzyme. The results indicated that the human lysine tRNA has the ability to be hyperprocessed but is structurally stabilized in spite of lacking base modifications. A comparative study suggested, moreover, that the acceptor-stem bases should take part in the stabilization of metazoan lysine tRNAs. Our data strongly suggest that the cloverleaf shape of other metazoan lysine tRNAs should also be stabilized by means of similar strategies to in the case of human tRNA(Lys3).
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PMID:Another cut for lysine tRNA: application of the hyperprocessing reaction reveals another stabilization strategy in metazoan lysine tRNAs. 1203 80

Dysfunction of cerebral cortex in autism is thought to involve alterations in inhibitory neurotransmission. Here, we screened, in prefrontal cortex (PFC) of 15 subjects diagnosed with autism and 15 matched controls the expression of 44 transcripts that are either preferentially expressed in gamma-aminobutyric acidergic interneurons of the mature cortex or important for the development of inhibitory circuitry. Significant alterations in the autism cohort included decreased expression (-45%) of RPP25 (15q24.1), which is located within the autism susceptibility locus, 15q22-26. RPP25, which encodes the 25 kDa subunit of ribonuclease P involved in tRNA and pre-ribosomal RNA processing, was developmentally regulated in cerebral cortex with peak levels of expression during late fetal development (human) or around birth (mouse). In the PFC, RPP25 chromatin showed high levels of histone H3-lysine 4 trimethylation, an epigenetic mark associated with transcriptional regulation. Unexpectedly, and in contrast to peripheral tissues, levels of RPP25 protein remained undetectable in fetal and adult cerebral cortex. Taken together, these findings suggest a potential role for the RPP25 gene transcript in the neurobiology of developmental brain disorders.
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PMID:RPP25 is developmentally regulated in prefrontal cortex and expressed at decreased levels in autism spectrum disorder. 2063 21

Dictyostelium discoideum nuclear RNase P is a ribonucleoprotein complex that displays similarities with its counterparts from higher eukaryotes such as the human enzyme, but at the same time it retains distinctive characteristics. In the present study, we report the molecular cloning and interaction details of DRpp29 and RNase P RNA, two subunits of the RNase P holoenzyme from D. discoideum. Electrophoretic mobility shift assays exhibited that DRpp29 binds specifically to the RNase P RNA subunit, a feature that was further confirmed by the molecular modeling of the DRpp29 structure. Moreover, deletion mutants of DRpp29 were constructed in order to investigate the domains of DRpp29 that contribute to and/or are responsible for the direct interaction with the D. discoideum RNase P RNA. A eukaryotic specific, lysine- and arginine-rich region was revealed, which seems to facilitate the interaction between these two subunits. Furthermore, we tested the ability of wild-type and mutant DRpp29 to form active RNase P enzymatic particles with the Escherichia coli RNase P RNA.
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PMID:Domain architecture of the DRpp29 protein and its interaction with the RNA subunit of Dictyostelium discoideum RNase P. 2108 28

RNA processing by ribonucleases and RNA modifying enzymes often involves sequential reactions of the same enzyme on a single precursor transcript. In Escherichia coli, processing of polycistronic tRNA precursors involves separation into individual pre-tRNAs by one of several ribonucleases followed by 5' end maturation by ribonuclease P. A notable exception are valine and lysine tRNAs encoded by three polycistronic precursors that follow a recently discovered pathway involving initial 3' to 5' directional processing by RNase P. Here, we show that the dicistronic precursor containing tRNAvalV and tRNAvalW undergoes accurate and efficient 3' to 5' directional processing by RNase P in vitro. Kinetic analyses reveal a distributive mechanism involving dissociation of the enzyme between the two cleavage steps. Directional processing is maintained despite swapping or duplicating the two tRNAs consistent with inhibition of processing by 3' trailer sequences. Structure-function studies identify a stem-loop in 5' leader of tRNAvalV that inhibits RNase P cleavage and further enforces directional processing. The results demonstrate that directional processing is an intrinsic property of RNase P and show how RNA sequence and structure context can modulate reaction rates in order to direct precursors along specific pathways.
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PMID:Distributive enzyme binding controlled by local RNA context results in 3' to 5' directional processing of dicistronic tRNA precursors by Escherichia coli ribonuclease P. 3049 57

17-beta-hydroxysteroid dehydrogenase 10 (HSD17B10) plays an important role in mitochondrial fatty acid metabolism and is also involved in mitochondrial tRNA maturation. HSD17B10 missense mutations cause HSD10 mitochondrial disease (HSD10MD). HSD17B10 with mutations identified from cases of HSD10MD show loss of function in dehydrogenase activity and mitochondrial tRNA maturation, resulting in mitochondrial dysfunction. It has also been implicated to play roles in the development of Alzheimer disease (AD) and tumorigenesis. Here, we found that HSD17B10 is a new substrate of NAD-dependent deacetylase Sirtuin 3 (SIRT3). HSD17B10 is acetylated at lysine residues K79, K99 and K105 by the acetyltransferase CBP, and the acetylation is reversed by SIRT3. HSD17B10 acetylation regulates its enzymatic activity and the formation of mitochondrial RNase P. Furthermore, HSD17B10 acetylation regulates the intracellular functions, affecting cell growth and cell resistance in response to stresses. Our results demonstrated that acetylation is an important regulation mechanism for HSD17B10 and may provide insight into interrupting the development of AD.
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PMID:Deacetylation of HSD17B10 by SIRT3 regulates cell growth and cell resistance under oxidative and starvation stresses. 3270 35