Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nearly 1 million interspersed Alu elements reside in the human genome. Alu retrotransposition is presumably mediated by full-length Alu transcripts synthesized by RNA polymerase III, while some polymerase III-synthesized Alu transcripts undergo 3'-processing and accumulate as small cytoplasmic (sc) RNAs of unknown function. Interspersed Alu sequences also reside in the untranslated regions of some mRNAs. The Alu sequence is related to a portion of the 7SL RNA component of signal recognition particle (SRP). This region of 7SL RNA together with 9- and 14-kDa polypeptides (SRP9/14) regulates translational elongation of ribosomes engaged by SRP. Here we characterize human (h) SRP9 and show that it, together with hSRP14 (SRP9/14), forms the activity previously identified as Alu RNA-binding protein (RBP). The primate-specific C-terminal tail of hSRP14 does not appreciably affect binding to scAlu RNA. Kd values for three Alu-homologous scRNAs were determined using Alu RBP (SRP9/14) purified from HeLa cells. The Alu region of 7SL, scAlu, and scB1 RNAs exhibited Kd values of 203 pM, 318 pM, and 1.8 nM, respectively. Finally, Alu RBP can bind with high affinity to synthetic mRNAs that contain interspersed Alus in their untranslated regions.
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PMID:Human signal recognition particle (SRP) Alu-associated protein also binds Alu interspersed repeat sequence RNAs. Characterization of human SRP9. 773 Mar 21

Nearly 1 000 000 copies of Alu interspersed elements comprise approximately 5% of human DNA. Alu elements cause gene disruptions by a process known as retrotransposition, in which dimeric Alu RNA is a presumed intermediate. Dimeric Alu transcripts are labile, giving rise to stable left monomeric scAlu RNAs whose levels are tightly regulated. Induction of Alu RNA by viral infection or cell stress leads to a dramatic increase in dimeric Alu transcripts, while scAlu RNA increases modestly. Each monomer of the dimeric Alu element shares sequence homology with the 7SL RNA component of the signal recognition particle (SRP). The SRP protein known as SRP9/14 is also found in a discrete complex with scAlu RNA, although whether dimeric Alu RNA is associated with SRP9/14 had been unknown. Here we show that antiserum to human SRP9 immunoprecipitates both scAlu RNA and dimeric Alu RNAs and that these RNPs accumulate after adenovirus infection, while levels of SRP9, SRP14, SRP54 and 7SL SRP RNA are unaffected. Dimeric Alu RNAs are also associated with the La protein, indicating that these are indeed nascent RNA polymerase III transcripts. This report documents that induced Alu transcripts are assembled into SRP9/14-containing RNPs in vivo while SRP levels are unchanged. Implications for Alu RNA metabolism and evolution are discussed.
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PMID:Monomeric scAlu and nascent dimeric Alu RNAs induced by adenovirus are assembled into SRP9/14-containing RNPs in HeLa cells. 893 67

In a rare occasion a single chromosomal locus was targeted twice by independent Alu-related retroposon insertions, and in both cases supported neuronal expression of the respective inserted genes encoding small non-protein coding RNAs (npcRNAs): BC200 RNA in anthropoid primates and G22 RNA in the Lorisoidea branch of prosimians. To avoid primate experimentation, we generated transgenic mice to study neuronal expression and protein binding partners for BC200 and G22 npcRNAs. The BC200 gene, with sufficient upstream flanking sequences, is expressed in transgenic mouse brain areas comparable to those in human brain, and G22 gene, with upstream flanks, has a similar expression pattern. However, when all upstream regions of the G22 gene were removed, expression was completely abolished, despite the presence of intact internal RNA polymerase III promoter elements. Transgenic BC200 RNA is transported into neuronal dendrites as it is in human brain. G22 RNA, almost twice as large as BC200 RNA, has a similar subcellular localization. Both transgenically expressed npcRNAs formed RNP complexes with poly(A) binding protein and the heterodimer SRP9/14, as does BC200 RNA in human. These observations strongly support the possibility that the independently exapted npcRNAs have similar functions, perhaps in translational regulation of dendritic protein biosynthesis in neurons of the respective primates.
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PMID:Two primate-specific small non-protein-coding RNAs in transgenic mice: neuronal expression, subcellular localization and binding partners. 1717 35

The human genome contains about 1.5 million Alu elements, which are transcribed into Alu RNAs by RNA polymerase III. Their expression is upregulated following stress and viral infection, and they associate with the SRP9/14 protein dimer in the cytoplasm forming Alu RNPs. Using cell-free translation, we have previously shown that Alu RNPs inhibit polysome formation. Here, we describe the mechanism of Alu RNP-mediated inhibition of translation initiation and demonstrate its effect on translation of cellular and viral RNAs. Both cap-dependent and IRES-mediated initiation is inhibited. Inhibition involves direct binding of SRP9/14 to 40S ribosomal subunits and requires Alu RNA as an assembly factor but its continuous association with 40S subunits is not required for inhibition. Binding of SRP9/14 to 40S prevents 48S complex formation by interfering with the recruitment of mRNA to 40S subunits. In cells, overexpression of Alu RNA decreases translation of reporter mRNAs and this effect is alleviated with a mutation that reduces its affinity for SRP9/14. Alu RNPs also inhibit the translation of cellular mRNAs resuming translation after stress and of viral mRNAs suggesting a role of Alu RNPs in adapting the translational output in response to stress and viral infection.
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PMID:Alu RNA regulates the cellular pool of active ribosomes by targeted delivery of SRP9/14 to 40S subunits. 2569 3