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
Query: EC:3.1.26.5 (
RNase P
)
1,348
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Subcellular fractionation of HeLa cells was carried out under gentle conditions to isolate enzymes that cleave RNA precursors in a specific manner. Four separate activities--cleavage of HeLa cell heterogeneous nuclear RNA, the HeLa cell 45S rRNA precursor, RNA . DNA hybrids (
RNase H
), and the Escherichia coli tRNATyr precursor (
RNase P
)--were revealed by these studies. The specificity and limited nature of these cleavages suggest that they are due to eukaryotic RNA-processing enzymes. The virtual absence of random nucleases from these enzymes was demonstrated by their inability to cleave the 8000-base early mRNA precursor of bacteriophage T7, E. coli 30S rRNA precursor, or HeLa cytoplasmic poly(A)-containing RNA.
...
PMID:Specific RNA-cleaving activities from HeLa cells. 693 Jun 39
ColE1 DNA replication is initiated by RNA II and inhibited by RNA I. Control of the replication occurs through the interaction between RNA I and RNA II. Therefore, RNases involved in the metabolism of RNA I and RNA II are expected to play a key role in the control of the ColE1 plasmid replication.
RNase H
, RNase E, RNase III,
RNase P
, and polynucleotide phosphorylase carry out the many specific reactions of the RNA metabolism.
...
PMID:RNases in ColE1 DNA metabolism. 890 10
Most antisense oligonucleotide experiments are performed with molecules containing
RNase H
-competent backbones. However,
RNase H
may cleave nontargeted mRNAs bound to only partially complementary oligonucleotides. Decreasing such "irrelevant cleavage" would be of critical importance to the ability of the antisense biotechnology to provide accurate assessment of gene function.
RNase P
is a ubiquitous endogenous cellular ribozyme whose function is to cleave the 5' terminus of precursor tRNAs to generate the mature tRNA. To recruit
RNase P
, complementary oligonucleotides called external guide sequences (EGS), which mimic structural features of precursor tRNA, were incorporated into an antisense 2'-O-methyl oligoribonucleotide targeted to the 3' region of the PKC-alpha mRNA. In T24 human bladder carcinoma cells, these EGSs, but not control sequences, were highly effective in downregulating PKC-alpha protein and mRNA expression. Furthermore, the downregulation is dependent on the presence of, and base sequence in, the T-loop. Similar observations were made with an EGS targeted to the bcl-xL mRNA.
...
PMID:Intracellular mRNA cleavage induced through activation of RNase P by nuclease-resistant external guide sequences. 1062 92
Antisense oligonucleotides are useful reagents for the suppression of gene expression. Their mechanism of action in eukaryotic cells appears to depend heavily on the activity of
RNase H
, a ubiquitous enzyme that cleaves the mRNA strand of an RNA-DNA duplex. However, the stringency requirements of
RNase H
are very low, and as little as a 5-base complementary region of oligomer to target may be sufficient to elicit
RNase H
activity. This would result in scission of nontargeted mRNAs, or what is known as "irrelevant cleavage." One strategy to reduce
RNase H
competency that has been employed is modification of the oligonucleotide backbone, replacing phosphodiester linkages with uncharged methylphosphonates, which are not
RNase H
competent. Another strategy involves replacement of deoxyribonucleic acid with 2'-O-alkylribonucleic acid. A third strategy, eliminating
RNase H
dependency entirely, requires activation of
RNase P
. The relative merits of these strategies will be discussed in the context of selective inhibition of gene function.
...
PMID:Is irrelevant cleavage the price of antisense efficacy? 1073 77