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

Yeast telomerase, the enzyme that adds a repeated DNA sequence to the ends of the chromosomes, consists of a 1157- nucleotide RNA (TLC1) plus several protein subunits: the telomerase reverse transcriptase Est2p, the regulatory subunit Est1p, the nonhomologous end-joining heterodimer Ku, and the seven Sm proteins involved in ribonucleoprotein (RNP) maturation. The RNA subunit provides the template for telomeric DNA synthesis. In addition, we have reported evidence that it serves as a flexible scaffold to tether the proteins into the complex. More generally, we consider the possibility that RNPs may be considered in three structural categories: (1) those that have specific structures determined in large part by the RNA, including RNase P, other ribozyme-protein complexes, and the ribosome; (2) those that have specific structures determined in large part by proteins, including many small nuclear RNPs (snRNPs) and small nucleolar RNPs (snoRNPs); and (3) flexible scaffolds, with no specific structure of the RNP as a whole, as exemplified by yeast telomerase. Other candidates for flexible scaffold structures are other telomerases, viral IRES (internal ribosome entry site) elements, tmRNA (transfer-messenger RNA), the SRP (signal recognition particle), and Xist and roX1 RNAs that alter chromatin structure to achieve dosage compensation.
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PMID:RNA as a flexible scaffold for proteins: yeast telomerase and beyond. 1738

Long non-coding transcripts from telomeres, called telomeric repeat-containing RNA (TERRA), were identified as blocking telomerase activity (TA), a telomere maintenance mechanism (TMM), in tumors. We expressed recombinant TERRA transcripts in tumor cell lines with TA and with alternative lengthening of telomeres (ALT) to study effects on TMM and cell growth. Adeno- and lentivirus constructs (AV and LV) were established for transient and stable expression of approximately 130 units of telomere hexanucleotide repeats under control of cytomegalovirus (CMV) and human RNase P RNA H1 (hH1) promoters with and without polyadenylation, respectively. Six human tumor cell lines either using telomerase or ALT were infected and analyzed for TA levels. Pre-infection cells using telomerase had 1%-3% of the TERRA expression levels of ALT cells. AV and LV expression of recombinant TERRA in telomerase positive cells showed a 1.3-2.6 fold increase in TERRA levels, and a decrease in TA of 25%-58%. Dominant-negative or small hairpin RNA (shRNA) viral expression against human telomerase reverse transcriptase (hTERT) results in senescence, not induced by TERRA expression. Population doubling time, cell viability and TL (telomere length) were not impacted by ectopic TERRA expression. Clonal growth was reduced by TERRA expression in TA but not ALT cell lines. ALT cells were not affected by treatments applied. Established cell models and tools may be used to better understand the role of TERRA in the cell, especially for targeting telomerase.
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PMID:Telomere Transcripts Target Telomerase in Human Cancer Cells. 2753 14

Recent studies show that nuclear RNase P is linked to chromatin structure and function. Thus, variants of this ribonucleoprotein (RNP) complex bind to chromatin of small noncoding RNA genes; integrate into initiation complexes of RNA polymerase (Pol) III; repress histone H3.3 nucleosome deposition; control tRNA and PIWI-interacting RNA (piRNA) gene clusters for genome defense; and respond to Werner syndrome helicase (WRN)-related replication stress and DNA double-strand breaks (DSBs). Likewise, the related RNase MRP and RMRP-TERT (telomerase reverse transcriptase) are implicated in RNA-dependent RNA polymerization for chromatin silencing, whereas the telomerase carries out RNA-dependent DNA polymerization for telomere lengthening. Remarkably, the four RNPs share several protein subunits, including two Alba-like chromatin proteins that possess DEAD-like and ATPase motifs found in chromatin modifiers and remodelers. Based on available data, RNase P and related RNPs act in transition processes of DNA to RNA and vice versa and connect these processes to genome preservation, including replication, DNA repair, and chromatin remodeling.
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PMID:Roles of RNase P and Its Subunits. 2869 48