Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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

The 5' processing of rat pre-tRNA(Lys) and a series of mutant derivatives by rat cytosolic RNase P was examined. In standard, non-kinetic assays, mutant precursors synthesized in vitro with 5' leader sequences of 10, 17, 24, 25, and 46 nucleotides were processed to approximately equal levels and yielded precisely cleaved 5' processed intermediates with the normal 7-base pair aminoacyl stems. The construct containing the tRNA(Lys) with the 46-nucleotide leader was modified by PCR to give a series of pre-tRNA(Lys) mutants designed to measure the effect on processing by (1) substituting the nucleotide at the +1 position, (2) pairing and unpairing the +1 and +72 bases, (3) elongating the aminoacyl stem, and (4) disrupting the helix of the aminoacyl stem. Comparative kinetic analyses revealed that changing the wild type +1G to A, C, or U was well tolerated by the RNase P provided that compensatory changes at +72 created a base pair or a G.U noncanonical pair. Mutants with elongated aminoacyl stems that were produced either by inserting an additional base pair at +3:a + 69:a or by pairing the -1A with a +73U, were processed to yield 7-base pair aminoacyl stems, but with different efficiencies. The efficiency seen with the double insertion mutant was higher than even the wild type precursor, but the -1A-U + 73 mutant was a relatively poor substrate. Disrupting the aminoacyl stem helix by introducing a +7G G + 66 mispairing or by inserting a single G at the +3:a position dramatically reduced the processing efficiency, although the position of cleavage occurred precisely at the wild type cleavage site. However, the single insertion of a C at the +69:a position resulted in an efficiently cleaved precursor, but permitted a minor, secondary cleavage within the leader between the -6 and -5 nucleotides in addition to the dominant wild type scission.
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PMID:The processing of wild type and mutant forms of rat nuclear pre-tRNA(Lys) by the homologous RNase P. 807 70

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

Previous analyses of eukaryotic pre-tRNAs processing have reported that 5'-cleavage by RNase P precedes 3'-maturation. Here we report that in contrast to all other yeast tRNAs analyzed to date, tRNA(Trp) undergoes 3'-maturation prior to 5'-cleavage. Despite its unusual processing pathway, pre-tRNA(Trp) resembles other pre-tRNAs, showing dependence on the essential Lsm proteins for normal processing and efficient association with the yeast La homolog, Lhp1p. tRNA(Trp) is also unusual in not requiring Lhp1p for 3' processing and stability. However, other Lhp1p-independent tRNAs, tRNA(2)(Lys) and tRNA(1)(Ile), follow the normal pathway of 5'-processing prior to 3-processing.
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PMID:3'-processing of yeast tRNATrp precedes 5'-processing. 1255 63

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

Accurate tRNA processing is crucial for human mitochondrial genome expression, but the mechanisms of mt-tRNA cleavage and the key enzymes involved in this process are poorly characterized. At least two activities are required for proper mt-tRNA maturation: RNase P cleaving precursor molecules at the 5' end and tRNase Z at the 3' end. In human mitochondria only RNase P has been identified so far. Using RT-PCR and northern blot analyses we found that silencing of the human ELAC2 gene results in impaired 3' end of mt-tRNAs. We demonstrate this for several mitochondrial tRNAs, encoded on both mtDNA strands, including tRNA (Val) , tRNA (Lys) , tRNA (Arg) , tRNA (Gly) , tRNA (Leu(UUR)) and tRNA (Glu) . The silencing of the MRPP1 gene that encodes a subunit of mtRNase P resulted in inhibition of both 5' and 3' processing. We also demonstrate the double mitochondrial/nuclear localization of the ELAC2 protein using immunofluorescence. Our results indicate that ELAC2 functions as a tRNase Z in human mitochondria and suggest that mt-tRNase Z preferentially cleaves molecules already processed by the proteinaceous mtRNase P.
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PMID:Involvement of human ELAC2 gene product in 3' end processing of mitochondrial tRNAs. 2159 7

Noncoding RNAs (ncRNAs) represent a big class of important RNA molecules. Given the large number of ncRNAs, identifying their functional sites is becoming one of the most important topics in the post-genomic era, but available computational methods are limited. For the above purpose, we previously presented a tertiary structure based method, Rsite, which first calculates the distance metrics defined in Methods with the tertiary structure of an ncRNA and then identifies the nucleotides located within the extreme points in the distance curve as the functional sites of the given ncRNA. However, the application of Rsite is largely limited because of limited RNA tertiary structures. Here we present a secondary structure based computational method, Rsite2, based on the observation that the secondary structure based nucleotide distance is strongly positively correlated with that derived from tertiary structure. This makes it reasonable to replace tertiary structure with secondary structure, which is much easier to obtain and process. Moreover, we applied Rsite2 to three ncRNAs (tRNA (Lys), Diels-Alder ribozyme, and RNase P) and a list of human mitochondria transcripts. The results show that Rsite2 works well with nearly equivalent accuracy as Rsite but is much more feasible and efficient. Finally, a web-server, the source codes, and the dataset of Rsite2 are available at http://www.cuialb.cn/rsite2.
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PMID:Rsite2: an efficient computational method to predict the functional sites of noncoding RNAs. 2675 1

The histone H3 variant H3.3 is a highly conserved and dynamic regulator of chromatin organization. Therefore, fully elucidating its nucleosome incorporation mechanisms is essential to understanding its functions in epigenetic inheritance. We previously identified the RNase P protein subunit, Rpp29, as a repressor of H3.3 chromatin assembly. Here, we use a biochemical assay to show that Rpp29 interacts with H3.3 through a sequence element in its own N terminus, and we identify a novel interaction with histone H2B at an adjacent site. The fact that archaeal Rpp29 does not include this N-terminal region suggests that it evolved to regulate eukaryote-specific functions. Oncogenic H3.3 mutations alter the H3.3-Rpp29 interaction, which suggests that they could dysregulate Rpp29 function in chromatin assembly. We also used KNS42 cells, an H3.3(G34V) pediatric high-grade glioma cell line, to show that Rpp29 1) represses H3.3 incorporation into transcriptionally active protein-coding, rRNA, and tRNA genes; 2) represses mRNA, protein expression, and antisense RNA; and 3) represses euchromatic post-translational modifications (PTMs) and promotes heterochromatic PTM deposition (i.e. histone H3 Lys-9 trimethylation (H3K9me3) and H3.1/2/3K27me3). Notably, we also found that K27me2 is increased and K36me1 decreased on H3.3(G34V), which suggests that Gly-34 mutations dysregulate Lys-27 and Lys-36 methylation in cis The fact that Rpp29 represses H3.3 chromatin assembly and sense and antisense RNA and promotes H3K9me3 and H3K27me3 suggests that Rpp29 regulates H3.3-mediated epigenetic mechanisms by processing a transcribed signal that recruits H3.3 to its incorporation sites.
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PMID:Rpp29 regulates histone H3.3 chromatin assembly through transcriptional mechanisms. 2992 82

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


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